DetailsCategory: DNA RNA and CellsPublished on Sunday, 09 February 2020 11:42Hits: 258

-- Robust efficacy with evidence of a dose response ---- 6/6 patients rescue-injection-free in cohort 1, with 3 patients at 52 weeks ---- 4/6 patients rescue-injection-free in cohort 2 (lower dose) at 24 weeks --

REDWOOD CITY, CA, USA I February 08, 2020 IAdverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today announced new interim clinical data from the OPTIC Phase 1 dose-ranging clinical trial of ADVM-022 intravitreal injection gene therapy. OPTIC includes treatment-experienced patients with wet age-related macular degeneration (AMD). The data are being presented today by David S. Boyer, M.D., senior partner, Retina-Vitreous Associates Medical Group and adjunct clinical professor of ophthalmology with the University of Southern California/Keck School of Medicine in Los Angeles, at the Angiogenesis, Exudation, and Degeneration 2020 Annual Meeting in Miami.

A copy of the presentation is available on the Adverum corporate website under Events and Presentations in the Investors section.

For the first time, data are being presented from patients in cohort 2 (n=6) at 24 weeks following treatment with a single intravitreal injection of a three-fold lower dose of ADVM-022 (2 x 10^11 vg/eye) compared to the cohort 1 dose (6 x 10^11 vg/eye).New data as detailed in the table below include:

OPTIC Phase 1 Clinical Trial Data:

I am very encouraged that this difficult-to-treat patient population enrolled in OPTIC is maintaining vision and anatomical improvements for an extended period of time, said David S. Boyer, M.D., senior partner, Retina-Vitreous Associates Medical Group and adjunct clinical professor of ophthalmology with the University of Southern California/Keck School of Medicine in Los Angeles, California. Additionally, ADVM-022continues to be safe and well tolerated, with ocular inflammation that is manageable with steroid eye drops. Patients with wet AMD and their caregivers carry a significant treatment burden from the current standard-of-care anti-VEGF injections, and real-world vision outcomes are suboptimal due to undertreatment. ADVM-022 as a one-time intravitreal injection therapy could transform the treatment paradigm for patients and their caregivers.

Aaron Osborne, MBBS, chief medical officer of Adverum, added, ADVM-022 has demonstrated a robust efficacy signal and evidence of a dose response in the OPTIC Phase 1 trial with data from 12 patients and two doses now available. Patients in cohort 2 received a three-fold lower dose of ADVM-022 than in cohort 1, and 4 of 6 of these patients are rescue injection-free through 24 weeks, whilst all 6 patients in cohort 1 remain rescue free with a median follow up of 50 weeks. OPTIC is progressing well, with the key objectives for cohorts 3 and 4 being to further evaluate dose response and to assess a 6-week prophylactic course of steroid eye drops instead of the 13-day oral steroid prophylaxis used in cohorts 1 and 2. We look forward to presenting clinical data from all four cohorts of OPTIC during this important year in the clinic for our novel gene therapy, ADVM-022.

KOL Discussion Tomorrow:In addition, Adverum will host an event with expert retinal specialists to discuss the OPTIC data presented at Angiogenesis and the potential opportunity for ADVM-022. The discussion will be held on Sunday, February 9, 2020 beginning at 10:00 am EST. The event will be webcast live from Adverums website at http://www.adverum.com in the Investors section under the Events and Presentations page. A replay of the webcast will be archived and available for replay following the event. A copy of the slide presentation will also available on the Adverum corporate website under Events and Presentations in the Investors section.

About the OPTIC Phase 1 Trial of ADVM-022 in Wet AMDThe multi-center, open-label, Phase 1, dose-ranging trial is designed to assess the safety and tolerability of a single intravitreal (IVT) administration of ADVM-022 in patients with wet AMD who are responsive to anti-vascular endothelial growth factor (VEGF) treatment. In cohort 1, patients (n=6) received ADVM-022 at a higher dose of 6 x 10^11 vg/eye and in cohort 2, patients (n=6) received ADVM-022 at a lower dose of 2 x 10^11 vg/eye. In cohort 3, patients (n=9) also are receiving a dose of 2 x 10^11 vg/eye and in cohort 4, patients (n=9) will receive a dose of 6 x 10^11 vg/eye. Patients in cohorts 3 and 4 will receive prophylactic steroid eye drops instead of oral steroids which were used in cohorts 1 and 2. The primary endpoint of the trial is the safety and tolerability of ADVM-022 after a single IVT administration. Secondary endpoints include changes in best-corrected visual acuity (BCVA), measurement of central retinal thickness (CRT), as well as mean number of anti-VEGF rescue injections and percentage of patients needing anti-VEGF rescue injections. Each patient enrolled will be followed for a total of two years.

Eight leading retinal centers acrossthe United States(U.S.) are participating in the OPTIC Phase 1 trial for ADVM-022. For more information on the OPTIC Phase 1 clinical trial of ADVM-022 in wet AMD, please visithttps://clinicaltrials.gov/ct2/show/NCT03748784.

About ADVM-022 Gene TherapyADVM-022 utilizes a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. ADVM-022 is administered as a one-time intravitreal injection, designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections, optimize patient compliance and improve vision outcomes for wet AMD and diabetic retinopathy patients.

In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for ADVM-022 for the treatment of this disease.

Adverum is currently evaluating ADVM-022 in the OPTIC study, a Phase 1 clinical trial in patients 50 years and older with wet AMD. Additionally, Adverum plans to submit an Investigational New Drug Application for ADVM-022 for the treatment of diabetic retinopathy to the U.S. Food and Drug Administration in the first half of 2020.

About Wet Age-related Macular Degeneration (AMD)Age-related macular degeneration (AMD) is a progressive disease affecting the macula, the region of the retina at the back of the eye responsible for central vision. In patients with wet AMD, an aggressive form of AMD, abnormal blood vessels grow underneath and into the retina. These abnormal blood vessels leak fluid and blood into and beneath the retina, causing vision loss.

Wet AMD is a leading cause of vision loss in patients over 60 years of age, with a prevalence of approximately 1.2 million individuals in the U.S. and 3 million worldwide. The incidence of new cases of wet AMD in the U.S. is approximately 150,000 to 200,000 annually, and this number is expected to grow significantly as the countrys population ages.

The current standard-of-care therapy for wet AMD is anti-VEGF intravitreal injections. These are effective but typically require eye injections every 4-12 weeks in order to maintain vision. Compliance with this regimen can be difficult for patients, caregivers, and healthcare systems, leading to undertreatment and resulting in loss of vision.

About Adverum BiotechnologiesAdverum Biotechnologies (Nasdaq: ADVM) is a clinical-stage gene therapy company targeting unmet medical needs in serious ocular and rare diseases. Adverum is evaluating its novel gene therapy candidate, ADVM-022, as a one-time, intravitreal injection for the treatment of its lead indication, wet age-related macular degeneration. For more information, please visit http://www.adverum.com.

SOURCE: Adverum Biotechnologies

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Adverum Biotechnologies Reports New Interim Data from Cohorts 1 and 2 of OPTIC Phase 1 Trial of ADVM-022 Intravitreal Gene Therapy for Wet AMD at...

Our lives have been transformed by the information age. But what's coming next is likely to be more profound, call it the genetic information age. We have mapped the human genome and in just the last few years we have learned to read and write DNA like software. And you're about to see a few breakthroughs-in-waiting that would transform human health. For a preview of this revolution in evolution we met George Church, a world leading geneticist, whose own DNA harbors many eccentricities and a few genes for genius.

We found George Church in here.

Cory Smith: Most of these are frozen George. Little bits of George that we have edited all in different tubes.

Church threw himself into his work, literally. His DNA is in many of the experiments in his lab at Harvard Medical School. The fully assembled George Church is 6'5" and 65. He helped pioneer mapping the human genome and editing DNA. Today, his lab is working to make humans immune to all viruses, eliminate genetic diseases, and reverse the effects of time.

Scott Pelley: One of the things your lab is working on is reversing aging.

George Church: That's right.

Scott Pelley: How is that possible?

George Church: Reversing aging is one of these things that is easy to dismiss to say either we don't need it or is impossible or both.

Scott Pelley: Oh, we need it.

George Church: Okay. We need it. That's good. We can agree on that. Well, aging reversal is something that's been proven about eight different ways in animals where you can get, you know, faster reaction times or, you know, cognitive or repair of damaged tissues.

Scott Pelley: Proven eight different ways. Why isn't this available?

George Church: It is available to mice.

In lucky mice, Church's lab added multiple genes that improved heart and kidney function and levels of blood sugar. Now he's trying it in spaniels.

Scott Pelley: So is this gene editing to achieve age reversal?

George Church: This is adding genes. So, it's not really editing genes. It's, the gene function is going down, and so we're boosting it back up by putting in extra copies of the genes.

Scott Pelley: What's the time horizon on age reversal in humans?

George Church: That's in clinical trials right now in dogs. And so, that veterinary product might be a couple years away and then that takes another ten years to get through the human clinical trials.

Human trials of a personal kind made George Church an unlikely candidate to alter human evolution. Growing up in Florida, Church was dyslexic, with attention deficit, and frequently knocked out by narcolepsy.

Scott Pelley: What was it that made you imagine that you could be a scientist?

George Church: The thing that got me hooked was probably the New York World's Fair in 1964. I thought this is the way we should all be living. When I went back to Florida, I said, "I've been robbed," you know? "Where is it all?" So, I said, "Well, if they're not going to provide it, then I'm gonna provide it for myself."

With work and repetition, he beat his disabilities and developed a genius for crystallography, a daunting technique that renders 3D images of molecules through X-rays and math. But in graduate school at Duke, at the age of 20, his mania for the basic structures of life didn't leave time for the basic structure of life.

Scott Pelley: You were homeless for a time.

George Church: Yeah. Briefly.

Scott Pelley: Six months.

George Church: Six months.

Scott Pelley: And where were you sleeping when you were homeless?

George Church: Well, yeah. I wasn't sleeping that much. I was mostly working. I'm narcoleptic. So, I fall asleep sitting up anyway.

His devotion to crystallography was his undoing at Duke.

George Church: I was extremely excited about the research I was doing. And so, I would put in 100-plus hours a week on research and then pretty much didn't do anything else.

Scott Pelley: Not go to class.

George Church: I wouldn't go to class. Yeah.

Duke kicked him out with this letter wishing him well in a field other than biology. But, it turned out, Harvard needed a crystallographer. George Church has been here nearly 40 years. He employs around 100 scientists, about half-and-half men and women.

Scott Pelley: Who do you hire?

George Church: I hire people that are self-selecting, they see our beacon from a distance away. There are a lot of people that are a little, you know, might be considered a little odd. "Neuroatypicals," some of us are called.

Scott Pelley: "Neuroatypical?"

George Church: Right.

Scott Pelley: Unusual brains?

George Church: Right, yeah.

Parastoo Khoshakhlagh: One thing about George that is very significant is that he sees what you can't even see in yourself.

Parastoo Khoshakhlagh and Alex Ng are among the "neuroatypicals." They're engineering human organ tissue.

Cory Smith: I think he tries to promote no fear of failure. The only fear is not to try at all.

Cory Smith's project sped up DNA editing from altering three genes at a time to 13,000 at a time. Eriona Hysolli went to Siberia with Church to extract DNA from the bones of wooly mammoths. She's editing the genes into elephant DNA to bring the mammoth back from extinction.

Eriona Hysolli: We are laying the foundations, perhaps, of de-extinction projects to come.

Scott Pelley: De-extinction.

Eriona Hysolli: Yes.

Scott Pelley: I'm not sure that's a word in the dictionary yet.

Eriona Hysolli: Well, if it isn't, it should be.

Scott Pelley: You know there are people watching this interview who think that is playing God.

George Church: Well, it's playing engineer. I mean, humans have been playing engineer since the dawn of time.

Scott Pelley: The point is, some people believe that you're mucking about in things that shouldn't be disturbed.

George Church: I completely agree that we need to be very cautious. And the more powerful, or the more rapidly-moving the technology, the more cautious we need to be, the bigger the conversation involving lots of different disciplines, religion, ethics, government, art, and so forth. And to see what it's unintended consequences might be.

Church anticipates consequences with a full time ethicist in the lab and he spends a good deal of time thinking about genetic equity. Believing that genetic technology must be available to all, not just those who can afford it.

We saw one of those technologies in the hands of Alex Ng and Parastoo Khoshakhlagh. They showed us what they call "mini-brains," tiny dots with millions of cells each. They've proven that cells from a patient can be grown into any organ tissue, in a matter of days, so drugs can be tested on that patient's unique genome.

Scott Pelley: You said that you got these cells from George's skin? How does that work?

Alex Ng: We have a way to reprogram essentially, skin cells, back into a stem cell state. And we have technologies where now we can differentiate them into tissue such as brain tissue.

Scott Pelley: So you went from George's skin cells, turned those into stem cells, and turned those into brain cells.

Alex Ng: Exactly. Exactly.

Scott Pelley: Simple as that.

Organs grown from a patient's own cells would eliminate the problem of rejection. Their goal is to prove the concept by growing full sized organs from Church's DNA.

George Church: It's considered more ethical for students to do experiments on their boss than vice versa and it's good to do it on me rather than some stranger because I'm as up to speed as you can be on the on the risks and the benefits. I'm properly consented. And I'm unlikely to change my mind.

Alex Ng: We have a joke in the lab, I mean, at some point, soon probably, we're going to have more of his cells outside of his body than he has himself.

Church's DNA is also used in experiments designed to make humans immune to all viruses.

George Church: We have a strategy by which we can make any cell or any organism resistant to all viruses by changing the genetic code. So if you change that code enough you now get something that is resistant to all viruses including viruses you never characterized before.

Scott Pelley: Because the viruses don't recognize it anymore?

George Church: They expect a certain code provided by the host that they replicate in. the virus would have to change so many parts of its DNA or RNA so that it can't change them all at once. So, it's not only dead. But it can't mutate to a new place where it could survive in a new host.

Yes, he's talking about the cure for the common cold and the end of waiting for organ transplants. It's long been known that pig organs could function in humans. Pig heart valves are routinely transplanted already. But pig viruses have kept surgeons from transplanting whole organs. Church's lab altered pig DNA and knocked out 62 pig viruses.

Scott Pelley: What organs might be transplanted from a pig to a human?

George Church: Heart, lung, kidney, liver, intestines, various parts of the eye, skin. All these things.

Scott Pelley: What's the time horizon on transplanting pig organs into human beings?

George Church: you know, two to five years to get into clinical trials. And then again it could take ten years to get through the clinical trials.

Church is a role model for the next generation. He has co-founded more than 35 startups. Recently, investors put $100 million into the pig organ work. Another Church startup is a dating app that compares DNA and screens out matches that would result in a child with an inherited disease.

George Church: You wouldn't find out who you're not compatible with. You'll just find out who you are compatible with.

Scott Pelley: You're suggesting that if everyone has their genome sequenced and the correct matches are made, that all of these diseases could be eliminated?

George Church: Right. It's 7,000 diseases. It's about 5% of the population. It's about a trillion dollars a year, worldwide.

Church sees one of his own genetic differences as an advantage. Narcolepsy lulls him several times a day. But he wakes, still in the conversation, often, discovering inspiration in his twilight zone.

Scott Pelley: If somebody had sequenced your genome some years ago, you might not have made the grade in some way.

George Church: I mean, that's true. I would hope that society sees the benefit of diversity not just ancestral diversity, but in our abilities. There's no perfect person.

Despite imperfection, Church has co-authored 527 scientific papers and holds more than 50 patents. Proof that great minds do not think alike.

The best science can tell, it was about 4 billion years ago that self-replicating molecules set off the spark of biology. Now, humans hold the tools of evolution, but George Church remains in awe of the original mystery: how chemistry became life.

Scott Pelley: Is the most amazing thing about life, then, that it happened at all?

George Church: It is amazing in our current state of ignorance. We don't even know if it ever happened ever in the rest of the universe. it's awe-inspiring to know that it either happened billions of times, or it never happened. Both of those are mind boggling. It's amazing that you can have such complex structures that make copies of themselves. But it's very hard to do that with machines that we've built. So, we're engineers. But we're rather poor engineers compared to the pseudo engineering that is biological evolution.

Produced by Henry Schuster. Associate producer, Rachael Morehouse. Broadcast associate, Ian Flickinger.

Continued here:
Harvard geneticist George Church's goal: to protect humans from viruses, genetic diseases, and aging - 60 Minutes - CBS News

Feng Zhang, a member of the McGovern Institute for Brain Research and an associate professor in the Departments of Brain and Cognitive Sciences and of Biological Engineering, has been named a winner of the 2017 Albany Medical Center Prize in Medicine and Biomedical Research.

Zhang, who is the Poitras Professor in Neuroscience at MIT and a core member of the Broad Institute, is recognized for his contributions to the development of CRISPR-Cas9 as a gene editing technology, which in the words of the prize announcement has revolutionized biomedical research and provided new hope for the treatment of genetic diseases and more.

The $500,000 prize has been given annually since 2001 to those who have altered the course of medical research, and is one of the largest prizes in medicine and science in the United States. Past recipients include eight Nobel Laureates.

In announcing the award, the Dean of Albany Medical College, Vincent Verdile, said: Rarely has such a recent discovery transformed an entire field of research, as CRISPR has in biological research. Its implications for biological processes, including human health and disease are promising and quite profound.

Zhang will share the prize with four other CRISPR researchers: Emmanuelle Charpentier of the Max Planck Institute; Jennifer Doudna of University of California at Berkeley; Luciano Marraffini of Rockefeller University; and Francisco Mojica of the University of Alicante.

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Feng Zhang to share Albany Medical Prize - MIT News

Jan. 24, 2020 06:00 UTC

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the Phase III IMvigor010 study evaluating Tecentriq (atezolizumab) as an adjuvant (after surgery) monotherapy treatment did not meet its primary endpoint of disease-free survival (DFS) compared to observation in people with muscle-invasive urothelial cancer (MIUC). Safety for Tecentriq appeared consistent with the known safety profile of the medicine, and no new safety signals were identified.

Reducing the risk that muscle-invasive urothelial cancer will recur after surgery is very difficult, and we are disappointed that we were not able to significantly prolong disease-free survival, said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. We remain committed to exploring the potential benefits of immunotherapy for more people with early cancers.

The goal in treating MIUC early is to reduce the risk of the disease recurring or spreading to other parts of the body. More treatment options following surgery are needed as approximately half of people with MIUC will develop a recurrence of their disease within two years of surgery.

In addition to ongoing Phase III studies in early and advanced bladder cancer, Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across genitourinary, skin, breast, gastrointestinal, gynecological and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMvigor010 study

IMvigor010 is a global Phase III, open-label, randomized, controlled study designed to evaluate the efficacy and safety of adjuvant treatment with Tecentriq compared with observation in 809 people with MIUC, who are at high risk for recurrence following resection. The primary endpoint is DFS as assessed by investigator, which is defined as the time from randomization to invasive urothelial cancer recurrence or death.

About bladder cancer

According to the American Cancer Society (ACS), it is estimated that more than 81,000 Americans will be diagnosed with bladder cancer in 2020. Urothelial cancer is the most common type of bladder cancer, accounting for about 90-95% of all cases. MIUC is a type of urothelial cancer that has spread into the muscle wall of the bladder, ureter, or renal pelvis. Approximately 25% of people newly diagnosed with bladder cancer are diagnosed with muscle-invasive disease, which is associated with a poorer prognosis than non-MIUC.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Tecentriq U.S. Bladder Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of bladder and urinary tract cancer called urothelial carcinoma. Tecentriq may be used when your bladder cancer:

The approval of Tecentriq in these patients is based on a study that measured response rate and duration of response. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

It is not known if Tecentriq is safe and effective in children.

Important Safety Information What is the most important information about Tecentriq? Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used alone include:

Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information about the benefits and side effects of Tecentriq.

Report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.Tecentriq.com for the Tecentriq full Prescribing Information for additional Important Safety Information.

About Genentech in personalized cancer immunotherapy

For more than 30 years, Genentech has been developing medicines with the goal to redefine treatment in oncology. Today, were investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer. The goal of PCI is to provide each person with a treatment tailored to harness his or her own immune system to fight cancer. Genentech is studying more than 10 cancer immunotherapy medicines across 70 clinical trials alone or in combination with other medicines. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit http://www.gene.com/cancer-immunotherapy.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200123005903/en/

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Genentech Provides an Update on Phase III Study of Tecentriq in People With Muscle-invasive Urothelial Cancer - BioSpace

The Division of Molecular Medicine and Gene Therapy is located at the Biomedical Center (BMC), Lund University, Sweden. Established as a joint venture between the Medical Faculty at Lund University and the Hematology Clinic at Lund University Hospital, our mission is to translate basic science to clinical applications.

Our research focuses on hematopoiesis, the continuous and dynamic process of blood cell formation. The laboratory consists of eight closely collaborating research groups that all share a common interest in investigating the properties of blood stem cellsto eventually understand and treat hematological disorders.

Five of our researchers belong to the Hemato-LinnExcellence Linnaeus Research Environment funded by The Swedish Research Council and Lund University. Several of the groups are engaged in StemTherapy, a Strategic Research Area for Stem Cells and Regenerative Medicine that is also supported by The Swedish Research Council.

Please welcome our new colleague MelissaIlsleyto the Flygare lab. Melissa joins our Division from theMater Research Institute, University of Queensland, Brisbane, Australia, where she's studied the transcriptional control of erythropoiesis.During her postdoc project, Melissa will be screening for therapeutic targets of Diamond Blackfan anemia.

Welcome to the Division of Molecular Medicine and Gene Therapy, Melissa.

Congratulations to Shubhranshu Debnath and all co-authors, whose work "Lentiviral vectors with cellular promoters correct the anemia and lethal bone marrow failure in a mouse model for Diamond-Blackfan anemia" has been accepted in Molecular Therapy.

In this study, the authorsdemonstrate the feasibility of lentiviral-based gene therapy in a mouse model of Diamond-Blackfan anemia (DBA), a rare inherited bone marrow failure disorder. Using lentiviral vectors with cellular promoters, Debnath et al. cured DBA in a mouse model of the disease and improved the safety profile following integration as characterised by a lower risk of insertional oncogenesis.These findings support the potential of clinical gene therapy as treatment option for DBA patients in the future.

Congratulations to all authors!

On May 11, Carolina Guibentifwill defend her thesis entitled"Modelling Human Developmental Hematopoiesis".

May 11 at9 am; Segerfalk Lecture Hall, BMC A10

Professor Nancy A. Speck,Perelman School of Medicine, University of Pennsylvania, USA

Associate Professor Niels-Bjarne Woods

Professor Jonas Larsson

Welcome!

Welcome to this months Stem Cell Talk, which will take place onWednesday April 19th, starting at 14:45 with fika atSegerfalkLecture Hall at A10.

Speaker:Kenichi Miharada

Title: Stressresponse and management in hematopoiesis

Welcome!

Please welcome our new colleaguesEmma Smith, Mayur Jain and MitsuyoshiSuzuki, who recently joined the Division of Molecular Medicine and Gene Therapy.

Emma Smith will be working in Stefan Karlsson's group as a staff scientist, where she will be involved in a collaborative project that aims to develop gene therapy as treatment option for patients suffering from the rare geneticlysosomal storage disorder Gaucher's disease.

Mayur Jain joined Sofie Singbrant Sderberg's group as a postdoctoral fellow. During his postdoc project, Mayur will be elucidating disease contributing factors in myeloproliferative disease, andinvestigatehow chronic anemia affects the ability of hematopoietic stem cells to provide a balanced blood production.

MitsuyoshiSuzuki joined the Miharada lab from Juntendo University in Tokyo, Japan. During his postdoc project, he will be clarifying therole of bile acid in fetal hematopoiesis and liver development.

Welcome to our Divison!

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Molecular Medicine and Gene Therapy | Medicinska ...

Research, published today in the journal Neurology, describes how mutations in a specific gene that codes for a neural growth factor appear to predict how quickly memory loss will progress in people with Alzheimer's disease.

Alzheimer's disease is the most common form of dementia in older adults. It is a degenerative condition, characterized by a steady loss of memory and a reduced ability to carry out daily activities.

Today, an estimated 5 million people in the United States are living with the disease.

The hallmark of Alzheimer's disease is a buildup of two types of protein: beta-amyloid plaques outside of nerve cells, and tau tangles within neurons.

Although these proteins appear to be involved in the pathology of Alzheimer's, little is known about why the condition begins and how it progresses. Early detection is still difficult, and treatment options are poor.

Because of the aging population in Western societies, the number of people with Alzheimer's is steadily rising. As a result of this, and together with the lack of successful pharmacological interventions, research focused on understanding the condition is vital.

Researchers from University of Wisconsin School of Medicine in Madison recently set out to investigate whether they could identify an early marker for Alzheimer's disease. They focused on brain-derived neurotrophic factor (BDNF), a protein coded by a gene of the same name.

BDNF is known to support nerve cells, helping them to grow, specialize, and survive. This makes it a good target for Alzheimer's research. Earlier research has not always found solid links between levels of BDNF and Alzheimer's, so this time, the team looked specifically at a gene mutation called the BDNF Val66Met allele, or simply Met allele.

In total, 1,023 participants - aged 55 on average - were included, and all were healthy but at risk of developing Alzheimer's. They were followed for a maximum of 13 years. At the start of the study, blood samples were taken to test for the Met allele mutation, and it was found to be present in 32 percent of the individuals.

All participants carried out cognitive and memory tests at the beginning of the trial and up to five more times throughout the study's duration. Also, 140 of them underwent neuroimaging to look for beta-amyloid plaques.

The data showed that those with the Met allele mutation lost cognitive and memory skills "more rapidly" when compared with those who did not have the mutation. Furthermore, individuals who carried both the mutation and plaques experienced an even quicker decline.

In verbal learning and memory tests, individuals without the gene mutation improved by 0.002 units per year, whereas those with the mutation worsened by 0.021 units each year.

"When there is no mutation, it is possible the BDNF gene, and the protein it produces are better able to be protective, thereby preserving memory and thinking skills. This is especially interesting because previous studies have shown that exercise can increase levels of BDNF.

It is critical for future studies to further investigate the role that the BDNF gene and protein have in beta-amyloid accumulation in the brain."

Study author Ozioma Okonkwo, Ph.D.

Because current treatment is most successful if given earlier in the disease's progression, this could be a vital part of the jigsaw. As Okonkwo says, "Because this gene can be detected before the symptoms of Alzheimer's start, and because this presymptomatic phase is thought to be a critical period for treatments that could delay or prevent the disease, it could be a great target for early treatments."

There are some shortfalls in the research. These include the fact that all participants were white, whereas various ethnicities are affected differently by the disease. For instance, African Americans appear to be more susceptible. Another shortfall of the study is that the beta-amyloid data were limited.

However, the study carries some weight because it involved a large number of participants, and the findings are sure to spark more research.

Learn about the link between Alzheimer's and vascular disease.

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Alzheimer's disease progression predicted by gene mutation ... - Medical News Today

May 4, 2017 A depiction of the double helical structure of DNA. Its four coding units (A, T, C, G) are color-coded in pink, orange, purple and yellow. Credit: NHGRI

Researchers investigating a form of adult-onset diabetes that shares features with the two better-known types of diabetes have discovered genetic influences that may offer clues to more accurate diagnosis and treatment.

Latent autoimmune diabetes in adults (LADA) is informally called "type 1.5 diabetes" because like type 1 diabetes (T1D), LADA is marked by circulating autoantibodies, an indicator that an overactive immune system is damaging the body's insulin-producing beta cells. But LADA also shares clinical features with type 2 diabetes (T2D), which tends to appear in adulthood. Also, as in T2D, LADA patients do not require insulin treatments when first diagnosed.

A study published April 25 in BMC Medicine uses genetic analysis to show that LADA is closer to T1D than to T2D. "Correctly diagnosing subtypes of diabetes is important, because it affects how physicians manage a patient's disease," said co-study leader Struan F.A. Grant, PhD, a genomics researcher at Children's Hospital of Philadelphia (CHOP). "If patients are misdiagnosed with the wrong type of diabetes, they may not receive the most effective medication."

Grant collaborated with European scientists, led by Richard David Leslie of the University of London, U.K.; and Bernhard O. Boehm, of Ulm University Medical Center, Germany and the Lee Kong Chian School of Medicine, a joint medical school of Imperial College London and Nanyang Technological University, Singapore.

Occurring when patients cannot produce their own insulin or are unable to properly process the insulin they do produce, diabetes is usually classified into two major types. T1D, formerly called juvenile diabetes, generally presents in childhood, but may also appear first in adults. T2D, formerly called non-insulin-dependent diabetes, typically appears in adults, but has been increasing over the past several decades in children and teens. Some 90 percent or more of all patients with diabetes are diagnosed with T2D.

Grant and many other researchers have discovered dozens of genetic regions that increase diabetes risk, usually with different sets of variants associated with T1D compared to T2D. The current study, the largest-ever genetic study of LADA, sought to determine how established T1D- or T2D-associated variants operate in the context of LADA.

The study team compared DNA from 978 LADA patients, all adults from the U.K. and Germany, to a control group of 1,057 children without diabetes. Another set of control samples came from 2,820 healthy adults in the U.K. All samples were from individuals of European ancestry.

The researchers calculated genetic risk scores to measure whether LADA patients had genetic profiles more similar to those of T1D or T2D patients. They found several T1D genetic regions associated with LADA, while relatively few T2D gene regions added to the risk of LADA. The genetic risk in LADA from T1D risk alleles was lower than in childhood-onset T1D, possibly accounting for the fact that LADA appears later in life.

One variant, located in TCF7L2, which Grant and colleagues showed in 2006 to be among the strongest genetic risk factors for T2D reported to date, had no role in LADA. "Our finding that LADA is genetically closer to T1D than to T2D suggests that some proportion of patients diagnosed as adults with type 2 diabetes may actually have late-onset type 1 diabetes," said Grant.

Grant said that larger studies are needed to further uncover genetic influences in the complex biology of diabetes, adding, "As we continue to integrate genetic findings with clinical characteristics, we may be able to more accurately classify diabetes subtypes to match patients with more effective treatments."

Explore further: More diabetes-associated, non-associated autoantibodies in T1D

More information: Rajashree Mishra et al, Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes, BMC Medicine (2017). DOI: 10.1186/s12916-017-0846-0

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Researchers investigating a form of adult-onset diabetes that shares features with the two better-known types of diabetes have discovered genetic influences that may offer clues to more accurate diagnosis and treatment.

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Worldwide, tens of millions of people are living with HIV. While scientists and medical professionals do not yet have a permanent cure for the virus, researchers have just made a breakthrough: they managed to eliminate the HIV-1 infection in mice.

According to the Centers for Disease Control and Prevention (CDC), more than 36 million people across the world are HIV positive, and approximately 1.2 million people in the United States live with the virus.

While there is currently no cure for the infection, scientists have just moved closer to finding one. Using a gene editing technology called "CRISPR/Cas9," the researchers successfully excised the HIV-1 provirus in three animal models.

A provirus is an inactive form of virus. It occurs when the virus has integrated into the genes of a cell. In the case of HIV, these host cells are the so-called CD4 cells - once the virus has been incorporated into the DNA of the CD4 cells, it replicates itself with each generation of CD4 cells.

The three mouse models used in the current research included a "humanized" model, in which the mice were genetically modified to have human immune cells, which were then infected with HIV-1.

The team was co-led by Dr. Wenhui Hu, Ph.D., associate professor in the Center for Metabolic Disease Research and the Department of Pathology at the Lewis Katz School of Medicine (LKSOM) at Temple University in Philadelphia, together with Kamel Khalili, Ph.D., Laura H. Carnell Professor and chair of the Department of Neuroscience at LKSOM, and Won-Bin Young, Ph.D, who just recently joined LKSOM.

The new study - published in the journal Molecular Therapy - builds on previous research by the same team, during which they used genetically modified rodents to demonstrate that their gene editing technology could eliminate the HIV-1-infected segments of DNA.

"Our new study is more comprehensive," Dr. Hu explains. "We confirmed the data from our previous work and have improved the efficiency of our gene editing strategy. We also show that the strategy is effective in two additional mouse models, one representing acute infection in mouse cells and the other representing chronic, or latent, infection in human cells."

Dr. Hu and team inactivated HIV-1, significantly reducing the RNA expression of viral genes in the organs and tissues of genetically modified mice.

Specifically, the RNA expression was reduced by approximately 60 to 95 percent.

The researchers then tested their findings by acutely infecting mice with EcoHIV - the equivalent of the HIV-1 in humans. Dr. Khalili explains the procedure:

"During acute infection, HIV actively replicates. With EcoHIV mice, we were able to investigate the ability of the CRISPR/Cas9 strategy to block viral replication and potentially prevent systemic infection."

The CRISPR/Cas9 method was up to 96 percent efficacious in eradicating EcoHIV in mice.

Finally, in the third model, mice received a transplant of human immune cells, including T cells, which were then infected with HIV-1.

One of the main reasons that a cure for HIV has yet to be discovered is the virus's ability to "hide" in the genomes of T cells, where it lives latently. This is why researchers applied the CRISPR/Cas9 technology to these mice with infected T cells.

After a single round of gene editing, the viral segments were excised from the human cells that had been integrated into the mouse tissues and organs. They removed the provirus from the mice's spleen, lungs, heart, colon, and brain after only one therapy injection.

The injection was with "quadruplex sgRNAs/saCas9 AAV-DJ/8" - an improved adeno-associated viral (AAV) vector.

AAV vectors are commonly used in gene therapy, but "the AAV-DJ/8 subtype combines multiple serotypes, giving us a broader range of cell targets for the delivery of our CRISPR/Cas9 system," Dr. Hu explains.

To assess the success of the genetic interventions, the team measured HIV-1 RNA levels using live bioluminescence imaging.

This is the first time that a team of researchers has managed to halt the replication of the HIV-1 virus and eliminate it completely from the infected cells in animals.

The team also provided the first evidence that HIV-1 can be successfully eradicated and full infection with the virus can be prevented using the CRISPR/Cas9 gene editing strategy.

The study was deemed "a significant step towards human clinical trials" by the authors, and the findings represent a breakthrough in the search for an HIV cure.

"The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease, in order to further demonstrate elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells. Our eventual goal is a clinical trial in human patients."

Kamel Khalili, Ph.D.

Learn how an HIV 'fingerprint' tool could greatly assist vaccine development.

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THURSDAY, May 4, 2017 (HealthDay News) -- The antioxidant resveratrol -- found in red wine, peanuts and berries -- might improve the health of blood vessels in people with type 2 diabetes, a small study suggests.

The study found that resveratrol supplements lessened artery stiffness in some people with type 2 diabetes. Stiffening of the arteries, called arteriosclerosis, raises the risk of heart attack and stroke.

"In treatment with resveratrol among people with diabetes, there was a trend toward improvement in the stiffness. And in people with higher stiffness there was more of a benefit," said lead researcher Dr. Naomi Hamburg. She is chief of the vascular biology section at Boston University School of Medicine.

While the research suggests there might be ways to improve blood vessel abnormalities in people with type 2 diabetes, it's too soon to recommend resveratrol for that purpose, said Hamburg.

"We would need a longer study to look at whether this is going to reduce heart attacks and stroke," she added. "But I think this is evidence to support future research."

For now, Hamburg said, "the overall recommendation is to have a diet that's rich in fruits and vegetables."

As you age, your arteries stiffen, which can lead to an increased risk of heart disease. In people with type 2 diabetes and obesity, this process starts earlier and can have more severe consequences, she said.

The body's largest artery is the aorta, which carries blood from the heart toward the rest of the body. For the study, the researchers measured the aortic thickness of 57 patients with type 2 diabetes (age 56 and obese, on average). The investigators also conducted tests to measure blood-vessel health.

Some patients were given resveratrol supplements, while the others were given a placebo. Overall, the study found a trend toward less aortic stiffness in participants taking resveratrol supplements, but it wasn't statistically significant.

However, in a subset of 23 patients who had an exceptionally stiff aorta at the start of the study, 100-milligram (mg) daily doses of resveratrol for two weeks reduced stiffness nearly 5 percent. That regimen was followed by 300-mg doses over two weeks, which decreased stiffness by 9 percent, the researchers said.

Aortic stiffness increased among those taking a placebo for four weeks, the researchers found.

In animal studies, Hamburg said, resveratrol has been shown to activate a gene (SIRT1) that appears to delay aging and development of several diseases.

To see if the same thing would happen in humans, the same researchers took samples from the blood-vessel linings of seven patients and looked at SIRT1 activity. They found that gene activity increased slightly after resveratrol supplementation.

This doesn't prove that reservatrol activates the longevity gene, only that there was an association. Still, another scientist welcomed the new findings.

"We know that people who drink red wine and eat nuts live longer, but why?" said Dr. Byron Lee, a professor of medicine at the University of California, San Francisco. "It's exciting to see scientists now starting to unravel this mystery."

This study shows that a natural antioxidant in these foods can reverse age-related changes in the arteries, said Lee, who wasn't involved in the study.

"Impressively, the effect was seen after just a few weeks of treatment. Who knows what more prolonged antioxidant treatment could do to the arteries and other organs," he said.

Many people obtain resveratrol in their daily diet. However, Hamburg pointed out that the doses of resveratrol used in the study were much greater than exists in a glass of red wine, a major dietary source of the antioxidant.

The study was funded by the U.S. National Heart, Lung, and Blood Institute and the U.S. National Center for Complementary and Integrative Health.

The results were scheduled for presentation Thursday at a meeting of the American Heart Association, in Minneapolis. The research should be considered preliminary until published in a peer-reviewed medical journal.

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KANNAPOLIS A person could be almost three times more likely to develop multiple sclerosis if they are carrying variants of two particular genes, according to the latest findings from scientists at Duke Health and The University of Texas Medical Branch at Galveston.

The finding, published in the March 23 issue of the journal Cell, could open the way for new tests to identify those at greatest risk of MS and autoimmune disorders, as well as the development of drugs, the researchers said.

The research used biospecimens from the MS cohort of the Measurement to Understand the Reclassification of Disease Of Cabarrus/Kannapolis ( MURDOCK ) Study. The MURDOCK Study is Duke Healths longitudinal clinical research study based at the North Carolina Research Campus in Kannapolis, N.C. The MURDOCK community registry and bio-repository includes more than 12,000 participants and nearly 460,000 biological specimens.

Multiple sclerosis is a major cause of neurological disease in younger adults between the ages of 20 and 50 and disproportionally affects women.

The disease causes the bodys own immune system to attack nerve cells in the spinal cord and brain, causing problems with vision, muscle control, balance and basic body functions. Other symptoms can occur, and could lead to permanent disability.

While treatable, current MS therapies have adverse side effects, as they focus on slowing the progression of the disease through suppression of the immune system. There is no cure for MS.

Our study identifies an interaction with a known MS risk gene to unlock a new MS candidate gene, and in doing so, establishing a novel mechanism that is associated with the risk of multiple sclerosis and other autoimmune diseases, said co-lead author Simon Gregory, Ph.D., director of Genomics and Epigenetics at the Duke Molecular Physiology Institute and principal investigator for the MURDOCK MS Study.

Gregory with colleagues at University of Texas Medical Branch, the University of California, Berkeley, and Case Western Reserve University found two particular DNA variants that appear to play a role in MS. One of these variants is in IL7R, a gene previously associated with MS, and the other in DDX39B, a gene not previously connected to the disease.

When the two are present in a persons genetic code, their interaction can lead to an over-production of a protein called sIL7R. That proteins interactions with the bodys immune system plays an important, but not completely understood, role in MS.

Researchers used MURDOCK biospecimens to examine the chromosomal differences between DDX39B and IL7R.

The researchers said this new information could potentially be used to craft new tests to diagnose multiple sclerosis, or to improve therapeutic toolkits to fight MS and other autoimmune disorders.

One could envision how this type of knowledge will someday lead to diagnose multiple sclerosis sooner and, now that we have promising therapies, a doctor could start the appropriate treatment more quickly. It is not out the realm of possibility to imagine a path for screening for other autoimmune diseases such as Type 1 Diabetes, said co-lead author Mariano Garcia-Blanco, M.D., Ph.D., professor and chair of the Department of Biochemistry and Molecular Biology at University of Texas Medical Branch.

In addition to Gregory and Garcia-Blanco, study authors include lead author Gaddiel Galarza, Farren B.S. Briggs, Irina Evsyukova, Geraldine Schott-Lerner, Edward M. Kennedy, Tinashe Nyanhete, Liuyang Wang, Laura Bergamaschi, Steven G. Widen, Georgia D. Tomaras, Dennis C. Ko, Shelton S. Bradrick and Lisa F. Barcellos.

The research was supported by the National Institutes of Health, National MS Society Pilot Award, Duke University Whitehead Scholarship, Ruth and A. Morris Williams Faculty Research Prize funds from Duke University School of Medicine, start-up funds from University of Texas Medical Branch and funds from Mr. Herman Stone and family for MS research.

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Ovarian cancer is a common form of cancer and a leading cause of cancer death among women. The genes we inherit affect our chances of developing ovarian cancer, and a new genomic study identifies 12 genetic variants associated with the risk.

The Centers for Disease Control and Prevention (CDC) report that almost 21,000 women in the United States were diagnosed with ovarian cancer in 2013, and more than 14,000 died from the disease.

Early detection of ovarian cancer is crucial in improving the patients' survival rate. If the cancer is diagnosed in the early stages - that is, before it has spread beyond the ovaries - the survival rate is estimated at 92 percent. However, according to the American Cancer Society, only 15 percent of ovarian cancers are diagnosed this early.

New research by an international team of scientists from the United Kingdom, the U.S., and Australia identifies 12 genetic variations that raise the likelihood of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer. It forms in the epithelium (the tissue) that covers the ovaries.

The results of the new genomic study were published in the journal Nature Genetics.

The new study was conducted as part of the OncoArray Consortium - a large genomic study looking at almost 450,000 samples in an attempt to identify the genetic background for most common cancers.

The OncoArray Consortium used a novel genotyping technique that allowed the researchers to identify nearly 500,000 single nucleotide polymorphisms (SNPs), which are the most common type of variation found in the human genome.

The inherited genetic architecture accounts for a significant portion of a woman's risk of developing EOC, the authors explain.

"We know that a woman's genetic makeup accounts for about one third of her risk of developing ovarian cancer. This is the inherited component of disease risk. We are less certain of environmental factors that increase our risk, but we do know that several factors reduce the risk of ovarian cancer, including taking the oral contraceptive pill, having your tubes tied, and having children."

Prof. Paul Pharoah, co-lead author

Mutations in the BRCA1 and BRCA2 genes make up 40 percent of this risk.

These faulty genes are quite rare - occurring in approximately 1 in 300 people - and correlate with a high incidence of ovarian and breast cancer.

Using data from the OncoArray Consortium, the new study examined the DNA of more than 25,000 people diagnosed with EOC, as well as genetic data from a control group of nearly 41,000 healthy individuals.

Additionally, the researchers investigated more than 31,000 people who had the BRCA1 and BRCA2 genetic mutations, almost 4,000 of whom had EOC.

The researchers located 12 new genetic variants associated with EOC risk. Additionally, the new study confirmed 18 previously identified variants that had been linked to the risk of developing EOC.

Overall, 6.5 percent of the inherited genetic risk of developing EOC is now known.

The first author of the study, Dr. Catherine Phelan from the Moffitt Cancer Center in Tampa, FL, explains what this percentage means:

"Ovarian cancer is clearly a very complex disease - even the 30 risk variants that we now know increase risk of developing the disease account for just a small fraction of the inherited component. We believe that there will likely be many more genetic variants involved, each with extremely small effects. Most of these are likely to be common, but some will be rare."

The authors also note that some women will have multiple risk-associated gene variants, but even combined, these still do not account for more than a 2.8 percent chance of developing ovarian cancer in their lifetimes.

To put this number into perspective, patients who are offered the option to have their ovaries surgically removed as a preventive measure most often have a lifetime risk of at least 10 percent.

However, the researchers also note that a combination of these genetic variants and being a carrier of the faulty BRCA1 and BRCA2 genes might sometimes be enough to call for preventive surgery.

"In some ways, the hard work starts now. We really have little idea of the functional effect these variants have at the molecular or cellular level and so there are few clues as to how they might affect risk. If we can understand how they work, we will be in a better position to treat - and possibly prevent - ovarian cancer."

Dr. Simon Gayther, study co-author

Learn how tumor DNA fragments help to predict ovarian cancer outcomes.

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Study finds 12 genetic variants that raise the risk of ovarian cancer - Medical News Today

Scientists have long sought a strategy for curing genetic diseases, but with just a few notable exceptions have succeeded only in their dreams. Now, though, researchers in China and Texas have taken a step toward making the fantasies a reality for all inherited diseases.

Using the gene-editing tool known as CRISPR/Cas9, the researchers have successfully edited disease-causing mutations out of viable human embryos. Other Chinese groups had previously reported editing human embryos that could not develop into a baby because they carried extra chromosomes, but this is the first report involving viable embryos (SN Online: 4/8/16; SN Online: 4/23/15).

In the new work, reported March 1 in Molecular Genetics and Genomics, Jianqiao Liu of Guangzhou Medical University in China and colleagues used embryos with a normal number of chromosomes. The embryos were created using eggs and sperm left over from in vitro fertilization treatments. In theory, the embryos could develop into a baby if implanted into a womans uterus.

Researchers in Sweden and England are also conducting gene-editing experiments on viable human embryos (SN: 10/29/16, p. 15), but those groups have not yet reported results.

Human germline editing wasnt realistic until CRISPR/Cas9 and other new gene editors came along, says R. Alta Charo, a bioethicist at the University of Wisconsin Law School in Madison. Weve now gotten to the point where its possible to imagine a day when it would be safe enough to be feasible. Charo was among the experts on a National Academies of Sciences and Medicine panel that in February issued an assessment of human gene editing. Altering human embryos, eggs, sperm or the cells that produce eggs and sperm would be permissible, provided there were no other alternatives and the experiments met other strict criteria, the panel concluded (SN: 3/18/17, p. 7).

Story continues below graphic

CRISPR/Cas9 is a tool for editing genes. A guide RNA shepherds the Cas9 enzyme to a specific stretch of DNA. Cas9 then cleaves the DNA to disable or repair a gene.

Illustrations: E. Otwell

Still, technical hurdles remain before CRISPR/Cas9 can cross into widespread use in treating patients.

CRISPR/Cas9 comes in two parts: a DNA-cutting enzyme called Cas9, and a guide RNA that directs Cas9 to cut at a specified location in DNA. Guide RNAs work a little like a GPS system, says David Edgell, a molecular biologist at Western University in London, Ontario. Given precise coordinates or a truly unique address, a good GPS should take you to the right place every time.

Scientists design guide RNAs so that they will carry Cas9 to only one stretch of about 20 bases (the information-carrying subunits of DNA) out of the entire 6 billion base pairs that make up the human genetic instruction book, or genome. But most 20-base locations in the human genome arent particularly distinctive. They are like Starbucks coffee shops: There are a lot of them and they are often similar enough that a GPS might get confused about which one you want to go to, says Edgell. Similarly, guide RNAs sometimes direct Cas9 to cut alternative, or off-target, sites that are a base or two different from the intended destination. Off-target cutting is a problem because such edits might damage or change genes in unexpected ways.

Its a major issue for sure, says Bruce Korf, a geneticist at the University of Alabama at Birmingham and president of the American College of Medical Genetics and Genomics Foundation. Doctors trying to correct one genetic defect in a patient want to be sure they arent accidentally introducing another.

But CRISPR/Cas9s propensity to cut undesired sites may be exaggerated, says Alasdair MacKenzie, a molecular biologist at the University of Aberdeen in Scotland. In experiments with mice, MacKenzie and colleagues limited how much Cas9 was produced in cells and made sure the enzyme didnt stick around after it made an edit. No off-target cuts were detected in any of the mice resulting from successfully edited embryos, MacKenzie and colleagues reported in November in Neuropeptides.

Other researchers have experimented with assembling the Cas9 and guide RNAs outside of the cell and then putting the preassembled protein-RNA complex into cells. Thats the strategy the Chinese researchers took in the new human embryoediting study. No off-target cuts were detected in that study either, although only one edited embryo was closely examined.

Other researchers have been tinkering with the genetic scissors to produce high-fidelity versions of Cas9 that are far less likely to cut at off-target sites in the first place.

When a guide RNA leads Cas9 to a site that isnt a perfect match, the enzyme can latch onto DNAs phosphate backbone and stabilize itself enough to make a cut, says Benjamin Kleinstiver, a biochemist in J. Keith Joungs lab at Harvard Medical School. By tweaking Cas9, Kleinstiver and colleagues essentially eliminated the enzymes ability to hold on at off-target sites, without greatly harming its on-target cutting ability.

Regular versions of Cas9 cut between two and 25 off-target sites for seven guide RNAs the researchers tested. But the high-fidelity Cas9 worked nearly flawlessly for those guides. For instance, high-fidelity Cas9 reduced off-target cutting from 25 sites to just one for one of the guide RNAs, the researchers reported in January 2016 in Nature. That single stray snip, however, could be a problem if the technology were to be used in patients.

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Snipping the wrong bit of DNA is a potential problem for gene editing. In recent experiments, researchers modified the Cas9 enzyme in a CRISPR/Cas9 system to create a high-fidelity version that reduced off-target cutting.

Source: B. Kleinstiver et al/Nature 2016

A group led by CRISPR/Cas9 pioneer Feng Zhang of the Broad Institute of MIT and Harvard tinkered with different parts of the Cas9 enzyme. That team also produced a cutter that rarely cleaved DNA at off-target sites, the team reported last year in Science.

Another problem for gene editing has been that it is good at disabling, or knocking out, genes that are causing a problem but not at replacing genes that have gone bad. Knocking out a gene is easy because all Cas9 has to do is cut the DNA. Cells generally respond by gluing the cut ends back together. But, like pieces of a broken vase, they rarely fit perfectly again. Small flaws introduced in the regluing can cause the problem gene to produce nonfunctional proteins. Knocking out genes may help fight Huntingtons disease and other genetic disorders caused by single, rogue versions of genes.

Many genetic diseases, such as cystic fibrosis or Tay-Sachs, are caused when people inherit two mutated, nonfunctional copies of the same gene. Knocking those genes out wont help. Instead, researchers need to insert undamaged versions of the genes to restore health. Inserting a gene starts with cutting the DNA, but instead of gluing the cut ends together, cells use a matching piece of DNA as a template to repair the damage.

In the new human embryo work, Liu and colleagues, including Wei-Hua Wang of the Houston Fertility Institute in Texas, first tested this type of repair on embryos with an extra set of chromosomes. Efficiency was low; about 10 to 20 percent of embryos contained the desired edits. Researchers had previously argued that extra chromosomes could interfere with the editing process, so Lius group also made embryos with the normal two copies of each chromosome (one from the father and one from the mother). Sperm from men that have genetic diseases common in China were used to fertilize eggs. In one experiment, Lius group made 10 embryos, two of which carried a mutation in the G6PD gene. Mutations in that gene can lead to a type of anemia.

Then the team injected Cas9 protein already leashed to its guide RNA, along with a separate piece of DNA that embryos could use as a template for repairing the mutant gene. G6PD mutations were repaired in both embryos. Since both of the two embryos had the repair, the researchers say they achieved 100 percent efficiency. But one embryo was a mosaic: It carried the fix in some but not all of its cells. Another experiment to repair mutations in the HBB gene, linked to blood disorders, worked with 50 percent efficiency, but with some other technical glitches.

Scientists dont know whether editing just some cells in an embryo will be enough to cure genetic diseases. For that reason, some researchers think it may be necessary to step back from embryos to edit the precursor cells that produce eggs and sperm, says Harvard University geneticist George Church. Precursor cells can produce many copies of themselves, so some could be tested to ensure that proper edits have been made with no off-target mutations. Properly edited cells would then be coaxed into forming sperm or eggs in lab dishes. Researchers have already succeeded in making viable sperm and eggs from reprogrammed mouse stem cells (SN: 11/12/16, p. 6). Precursors of human sperm and eggs have also been grown in lab dishes (SN Online: 12/24/14), but researchers have yet to report making viable human embryos from such cells.

The technology to reliably and safely edit human germline cells will probably require several more years of development, researchers say.

Germline editing as altering embryos, eggs and sperm or their precursors is known probably wont be the first way CRISPR/Cas9 is used to tackle genetic diseases. Doctors are already planning experiments to edit genes in body cells of patients. Those experiments come with fewer ethical questions but have their own hurdles, researchers say.

We still have a few years to go, says MacKenzie, but Ive never been so hopeful as I am now of the capacity of this technology to change peoples lives.

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Egyptian Eman Ahmed, 36, who is in Mumbai for weight-reduction surgery, could be the first and only person in the world with a rare gene defect that causes severe obesity. Agene study revealed that a mutation in the gene which instructs a protein involved in the regulation of body weight, was causing the weight gain.

The genetic study, conducted by Core Diagnostics, to analyse 91 kinds of genes, isolated with obesity related syndromes was analysed by physicians and metabolism experts in USA, UK and India. Dr Muffazal Lakdawala, Emans treating doctor and bariatric surgeon at Saifee Hospital said Emans case is a medical miracle since patients suffering from monogenic disorders dont usually cross adolescence. Leptin hormone comes from fat tissues and signals the brain about depleting fat stores. In Emans case, the defective docking station in the brain that leptin plugs into doesnt receive any signals. As a result, Emans brain has perceived that she is constantly starving and that led her to constantly feel hungry, eat food, store it as fat and conserve energy, said Dr Lakdawala.

While two major gene defects were diagnosed, the cause of Emans obesity is a mutation in the leptin receptor protein (LEPR) gene. The variant has been previously detected in one individual in research setting by Personalized Diabetes Medicine Program, University of Maryland School of Medicine, and has been classified as a variant of uncertain significance (VUS). However, in Emans case this has assumed pathologic consequences leading to her obesity. Eman is the only one in the world with this gene defect causing obesity, said doctors from the hospital.

Mutations in this gene have been associated with an autosomal recessive disorder causing obesity and pituitary dysfunction. Leptin receptor deficiency leads to a disorder which is associated with excessive hunger, massive weight gain, and reduced production of hormones that direct sexual development. There is currently no specific treatment for this condition. However, a drug called MC4R Agonist, only available with one pharmaceutical company in the US, might help Eman. The drug has been tested on three paediatric patients and Eman will be the only adult case if she undergoes treatment. The plan is to track her weight loss for six months and then take a call on changing the line of treatment once her condition stabilises, added Dr Lakdawala.

Doctors said the drugs may be able, at least partially, bypass the signaling block in the brain but its too early to say if there will be a successful outcome. So if she has access to these drugs and they are effective then we have a solution. If not, then she may need a more radical surgery which causes malabsorption (process in which intestine cant adequately absorb certain nutrients into the bloodstream, said a doctor.

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Worlds heaviest woman Eman Ahmed loses 140kg in 5 weeks in India, weighs 358kg

Eman Ahmed vs Daulatram Jogawat: Two obese patients with different treatment

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Rare genetic mutation made Egyptian Eman the heaviest, says study - Hindustan Times

Theres a profound disconnect between what the latest gene-editing methods can do to increase yields and enhance crop disease and stress resistance and the trickle of such improved crops actually getting out into farmers fields.

The first generation of genetically modified (GM) crops has been remarkably successful. The whole world eats food containing ingredients derived from GM crops and feeds them to its myriad agricultural animals and pets. Despite many dire predictions of long-term negative health effects, a quarter century has passed and none have materialized.1 This remarkably clean track record should have assuaged public fears and assured the rapid development and adoption of GM crops of all kinds.

But it hasnt.

Decades after four major commodity biotech crops corn, soybeans, cotton and canola were introduced and rapidly soared to near market saturation in the countries that permitted their cultivation, the number of new GM crops being released to farmers remains tiny.

[Editors note: This article is part one of a four-part series on the progress of agricultural biotechnology.]

Yet the need for higher yielding, disease-resistant and stress-tolerant crops grows with each passing year. The pressures of population growth and climate warming are already outpacing the speed with which conventional breeding practices are expanding the global food supply.2 Land and water availability are rapidly becoming limiting, hence the focus is sharply on the intensification of agriculture.3 But the breeding methods that fueled the spectacular advances in agricultural productivity over the 20th century are near exhaustion.

Over the same period, knowledge of plant physiology and genetics has grown at an explosive pace, as has the technology for identifying and modifying genes of agronomic interest. We know vastly more about what genes do and how plant genomes change both naturally and under human intervention than we did even when the first GM crops were introduced in 1996.4

The recent invention and rapid development of gene- or genome-editing technology (aka SSN or sequence-specific nuclease technology) has facilitated a quantum leap in the ease and precision of genetic intervention, positioning researchers to accelerate the increase in crop yields and to make crop plants more resilient to the biotic and abiotic stresses exacerbated by climate warming.5

Yet just a few of the crops that need to be improved are being improved using the latest techniques and of those, only a few reach farmers each year. To understand this deep disconnect between what can be done to improve crops using modern molecular techniques and what is being done requires a look at the tangle of issues around GM technology at the interface between science, business and society.

In this four-part series, I first examine the factors that led to the disconnect between what can be done and what is being done. I then review both the successes and failures of the first generation of GM crops modified using recombinant DNA (rDNA) technology. I next introduce the new gene-editing technologies and what they promise. And finally, I take a look at the regulatory, political and business decisions that actually determine what gets out of research laboratories and into farmers fields. The entire essay will be available as a single publication following the completion of this series.

Part 1: The origins of the disconnect between the science and the farmer

Public resistance to innovation is not unusual, but hardly universal. People line up for the newest Apple iPhone, but have to be persuaded to try a GM apple that doesnt turn brown. Resistance generally subsides as a technology is widely adopted and proves harmless. GM technology in medicine, for example, is now broadly accepted, be it human insulin or any of the many new protein-based therapeutics. But the controversies around GM crops have persisted, and indeed intensified through the deliberate vilification efforts of both individuals and organizations.6,7

According to polls, the public remains largely ignorant of what GM organisms (GMOs) are and of how modern molecular methods fit into the long history of crop improvement.8 Because fear-based disinformation strategies are so effective, what has grown instead is the widespread conviction that GMOs are bad, meaning variously that they are harmful to health, unnatural, or produced by big biotech companies that unfairly exploit farmers.7,9

Part of the problem is that public awareness of genetic modification in agriculture is recent, arguably dating back only to the late 1980s when controversies erupted over field testing of the so-called ice-minus bacterium modified to eliminate a protein that promotes ice formation on the leaves of strawberries.10 Yet in a strictly scientific context, genetic modification denotes the entire spectrum of human interventions in the genetics of other organisms over more than 10 millenia.11

For crop plants, these encompass domestication, breeding, mutation breeding and, most recently, genetic improvement by molecular techniques. All involve genetic changes, aka mutations. Domestication and conventional plant breeding rely on organisms inherent genetic variation.

Direct genetic manipulation of crop plants using chemical and radiation mutagenesis (mutation breeding) dates back to the 1930s.12 But even now, few people other than plant breeders are aware that crops have long been improved through deliberate efforts to induce new mutations using both chemicals and irradiation. So today, it is the general understanding that genetically modified organisms (GMOs) are only those that have been modified by molecular methods. That is, most people think genetic modification is quite new.

And then theres what the regulators built

As if this were not sufficiently problematic, the way in which the regulatory environment evolved reinforced suspicions about GM safety. Early efforts to regulate the commercial introduction of GM crops emphasized the need to regulate new crop traits rather than the particular method by which they were introduced. But thats not what happened.

Starting from the beginning of the regulatory activities in the late 1980s, the U.S. agencies that oversee GM organisms have regulated only organisms modified by molecular methods and theyve regulated all of them, without regard to either nature of the organism or the trait that was added.13 This has been true of the US Department of Agriculture (USDA) and the Environmental Protection Agency (EPA), although the Food and Drug Administration has generally followed its practice of post-market oversight. None of the agencies subjected new crop varieties produced by the older methods of chemical and radiation mutagenesis to regulatory oversight.

Complying with the regulatory requirements proved not only time consuming and prohibitively expensive to developers,14 but also reinforced the altogether unfounded popular conviction that molecular methodology is dangerous. Both negative popular views of GM foods and the high regulatory costs associated with their introduction have shaped the present availability of GMOs in agriculture. Indeed, it is virtually impossible to understand the contemporary paucity of GM crop varieties without considering both regulatory and acceptance issues.

The recent development of gene-editing methods has led to a new round of public and bureaucratic controversy worldwide over what should be classified as a GMO and subject to regulatory oversight. Because gene-editing techniques15 introduce the same kinds of mutations as the older mutagenesis methods, crops modified by gene editing can be indistinguishable at the molecular level from those improved by mutation breeding.

Mutation breeding has been in safe use for a century, hence there is no scientifically defensible rationale for imposing regulations on crops with the same kinds of genetic changes produced by the new, far more precise methods. This is being recognized in some countries by decreasing the regulatory burden on certain types of crop modifications produced by gene-editing techniques.

However, in 2018 the European Court of Justice ruled that gene-edited crops should undergo the same level of regulatory scrutiny as crops modified by older molecular methods.16 As they have over the past 4 decades, the outcome of such regulatory decisions will profoundly influence the kinds of genetic improvements that will be undertaken and actually become available to farmers and consumers.

Thus both public opinion and regulatory practices have made major contributions to the disconnect between the modern science of crop improvement and the farmer.

1EC (2010). A decade of EUfunded GMO research (20012010). European Commission https://ec.europa.eu/research/biosociety/pdf/a_decade_of_eu-funded_gmo_research.pdf; NASEM (2016). Genetically Engineered Crops: Experiences and Prospects. National Academies of Sciences, Engineering, and Medicine 978-0-309-43735-6 http://www.nap.edu/catalog/23395/genetically-engineered-crops-experiences-and-prospects

2Ray DK et al. (2013). Yield trends are insufficient to double global crop production by 2050. PloS One 8:e66428.

3Tilman D et al. (2011). Global food demand and the sustainable intensification of agriculture. Proc Natl Acad Sci USA 108:20260-4.

4Richroch AE (2013). Assessment of GE food safety using -omics techniques and long-term animal feeding studies. New Biotechnol 30:351-54; Fedoroff NV (2013). Plant transposons and genome dynamics in evolution. (Wiley-Blackwell, Oxford, UK), p.212; Anderson JE et al. (2016). Genomic variation and DNA repair associated with soybean transgenesis: a comparison to cultivars and mutagenized plants. BMC Biotechnol 16:41.

5Podevin N et al. (2013). Site-directed nucleases: a paradigm shift in predictable, knowledge-based plant breeding. Trends Biotechnol 31:375-83; Zhang D et al. (2016). Targeted gene manipulation in plants using the CRISPR/Cas technology. J Genet Genomics 43:251-62; Zhang Y et al. (2019). The emerging and uncultivated potential of CRISPR technology in plant science. Nature Plants 5:778-94.

6Apel A (2010). The costly benefits of opposing agricultural biotechnology. New Biotechnol 27:635-40.

7Ryan CD et al. (2019). Monetizing disinformation in the attention economy: The case of genetically modified organisms (GMOs). European Management J 38:7-18.

8Funk C et al. (2015). Public and scientists views on science and society. Pew Research Center http://www.pewinternet.org/2015/01/29/public-and-scientists-views-on-science-and-society/

9Funk C and Kennedy B (2016). Public opinion about genetically modified foods and trust in scientists connected with these foods. Pew Research Center http://www.pewinternet.org/2016/12/01/public-opinion-about-genetically-modified-foods-and-trust-in-scientists-connected-with-these-foods/

10Palca J (1986). Ice-minus bacteria: Further snag and further delay. Nature 320:2.

11Fedoroff NV (2015). Food in a future of 10 billion. Agricult Food Security 4:11.

12Ahloowalia B et al. (2004). Global impact of mutation-derived varieties. Euphytica 135:187-204.

13Fedoroff NV (2013). Will common sense prevail? Trends Genet 29:188-9; Wolt JD et al. (2016). The regulatory status of genomeedited crops. Plant Biotechnol J 14:510-8; Van Eenennaam A and Fedoroff N. How the federal government can get biotech regulation right. Des Moines Register, 1 March 2018

14McDougall P (2011). The cost and time involved in the discovery, development and authorisation of a new plant biotechnology derived trait. Crop Life International https://croplife.org/plant-biotechnology/regulatory-2/cost-of-bringing-a-biotech-crop-to-market/

15Kleter GA et al. (2019). Gene-edited crops: towards a harmonized safety assessment. Trends Biotechnol 37:443-7.

16Kupferschmidt K (2018). EU verdict on CRISPR crops dismays scientists. Science 361:435.

Nina V. Fedoroff is an Emeritus Evan Pugh Professor atPenn State University

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Viewpoint: How consumer fear and misguided regulation limit the progress of crop biotechnology - Genetic Literacy Project

A new international project aims to enroll 500 COVID-19 patients to search for genetic mutations that make some people more vulnerable to severe infection.

HHMI scientists are joining many of their colleagues worldwide in working to combat the new coronavirus.Theyre developing diagnostic testing, understanding the viruss basic biology, modeling the epidemiology, and developing potential therapies or vaccines. Over the next several weeks, we will be sharing stories of some of this work.

Hundreds of clinicians worldwide are banding together in an effort to study some types ofseverecases of the new coronavirus disease.

The project, led by Howard Hughes Medical Institute (HHMI) Investigator Jean-Laurent Casanova at The Rockefeller University, seeks to identify genetic errors that make some younger patients especially vulnerable to the virus that causes COVID-19, the infectious respiratory illness also known as coronavirus disease 2019.

Casanova aims to enroll 500 patients internationally who meet three broad criteria: theyre less than 50 years old, have been diagnosed with COVID-19 and admitted to an intensive care unit, and have no serious underlying illnesses, such as diabetes, heart disease, or lung disease.

By studying these patients' DNA, scientists may pinpoint genetic mutations that make some people more susceptible to infection. Such information could one day help doctors identify people who are most at risk of developing severe coronavirus disease, says Casanova, a pediatrician at Rockefeller. It could also offer clues for scientists searching for new therapeutics. For example, if patients cells arent making enough of a particular molecule, doctors may be able to offer a supplement as treatment.

Were going to try to find the genetic basis of severe coronavirus infection in young people.

Jean-Laurent Casanova, HHMI Investigator at The Rockefeller University

That day may still be years away. This is not a short-term effort, Casanova says. Some scientists have hypothesized that COVID-19 might be a seasonal illness, with infections ebbing in the spring and summer, and then returning in the fall. But Casanovas team is optimistic. They have already begun enrolling patients and have started sequencing their exomes spelling out all of the DNA letters in every gene in a persons genome. Were going to try to find the genetic basis of severe coronavirus infection in young people.

Late last year, when the first coronavirus infections began cropping up in China, Casanova started reaching out to his colleagues there. Though the most severe cases seemed to concentrate among older adults and those with other conditions, Casanova was interested in the outliers kids and young adults hit hard by the illness who didnt have any of the usual risk factors, such as age or underlying illness.

His team kicked off a new project to study these mysterious cases, and in January just weeks after the Wuhan outbreak began enrolling patients. Clinicians mailed patient blood and DNA to his lab, and researchers there and elsewhere began processing samples the first steps needed for scientists to peer into patients genomes. Now, the project is global, and Casanova is collaborating with scientists and healthcare workers from Europe to Africa, Asia, and Oceania.

We will recruit children and adults <50 yo without risk factor admitted to ICU for idiopathic #COVID19. We will test the hypothesis that they carry inborn errors of immunity to this virus. Please refer patients to @casanova_lab and please RT. pic.twitter.com/DXPoFKieEy

Hunting for the genetic underpinnings of severe infectious diseases is nothing new for Casanovas team. What were doing with coronavirus is what my lab has been doing for 25 years with other infections, he says.

They look for weak spots in peoples immune systems small genetic changes that make people more vulnerable to disease. His group has previously searched the genomes of patients infected with viruses, bacteria, fungi, and even parasites. The infection closest to COVID-19 his team has studied is severe influenza pneumonitis, for which theyve discovered three genetic links. Theyve also identified specific genetic errors that can predispose patients with herpes to viral encephalitis. And theyve found that children with mutations in an immunity gene called IFN-gamma are vulnerable to the bacteria that cause tuberculosis. These children make low levels of the IFN-gamma protein, which is critical for fighting off bacterial infections.

Casanovas team has put these findings to use clinically. For example, the researchers have shown that tuberculosis patients with these genetic errors can benefit from treatment with IFN-gamma. Hes hoping to identify problematic genes in patients with severe coronavirus infection that can bring similar clinical gains. These genes could tell scientists which cellular defenses are crucial for warding off COVID-19 and pave the way for understanding whether such defenses are derailed in older adults or patients with an underlying medical condition.

In the US and around the world, severe coronavirus disease seems to hit older patients hardest, though scientists have reported some country-to-country variation. As of March 24, more than 44,000 confirmed and presumptive positive cases have been reported in the US. Fatality has been highest in people over 85 years old, according to a recent report from the Centers for Disease Control and Prevention (CDC). Though young people may be more susceptible than scientists once suspected,the older you are, the higher the likelihood you have a severe form of the disease, Casanova says.

Last week, Rockefeller closed all labs except those working on the coronavirus, and Casanova whittled his team to a skeleton crew of about eight people down from 35 who rotate so there is only one person per room at a time. He and his lab members are following CDC recommendations, and taking protective measures to keep themselves and others safe, including social distancing, washing hands, and disinfecting surfaces. Theyve also taken to Twitter to get the word out about their work. A tweet posted from Casanovas lab last week about recruiting new patients to their study has since been retweeted more than 400 times.

Soon, theyll be testing their genetic theory on a pandemic thats occurring in real time. Im grateful weve been able to start this new project so quickly, he says. God willing, it will be of clinical usein two or three years.

Follow the Casanova lab on Twitter (@casanova_lab) to learn the latest about their work. Doctors interested in enrolling patients in the study can contact Jean-Laurent Casanova at jean-laurent.casanova@rockefeller.edu.

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Patients with Severe Forms of Coronavirus Disease Could Offer Clues to Treatment - Howard Hughes Medical Institute

Triglycerides, those fats that seem to be the bane of any diet, remain a mystery for many researchers. Plenty of them are in Big Macs, deep pan pizza and the like, but some are a necessity to fuel the body for daily activities.Researchers Mark Castleberry, a doctoral student, and professor Sean Davidson, both in the UC College of Medicine, have found a way to produce in the laboratory a human protein produced in the liver known as Apolipoprotein A5 (APOA 5). It plays an important role in metabolizing and clearing excess levels of triglycerides from the bloodstream.

We are really interested in understanding triglycerides because hypertriglyceridemia too much fat in your blood is a big factor leading to cardiovascular disease, diabetes, obesity and other health concerns, explains Davidson, who holds appointments in UCs departments of Pathology and Laboratory Medicine and Molecular Genetics, Biochemistry and Microbiology. When you have a lot of fat that is hanging around in your circulation its important to clear as much of it out as soon as possible.

APOA5 is highly involved in how fast triglycerides get taken out of your circulation, says Davidson, who has a doctorate in biochemistry. The more APOA5 you have the faster the triglyceride is removed. Everybody agrees it is an important protein but scientists dont know much about its structure or how it does what it does. If we could figure out how it works we could come up with a drug that uses the same mechanism or trigger it to work better.

Castleberry says researchers inserted a human gene coded by DNA into bacteria genetically engineered to produce human proteins. Once those proteins were produced they were removed from the host and purified for use in studies at the lab bench and in mouse models.

We can quickly make a much greater amount of this protein using bacterial production than if we tried to isolate it from blood in humans, explains Castleberry. The mice in this study were basically fed a large bowl of fat and triglycerides.

We could analyze their blood after we fed them and observe the level of fat change as they digested the meal, said Castleberry. We were able to give our protein to the mice that had that fatty meal and rapidly clear the triglycerides that would have accumulated in their blood."ReferenceCastleberry et al. (2020) Functional recombinant apolipoprotein A5 that is stable at high concentrations at physiological pH. The Journal of Lipid Research. DOI: https://doi.org/10.1194/jlr.D119000103

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Fat Busting Proteins Produced In the Laboratory - Technology Networks

The coronavirus pandemic has led to a spike in sales of products, includinghand sanitizer, toilet paper and pasta.

More than likely, however, there is no need to buy too much of anything, Dr. Amy Edwards, a pediatric infectious disease specialist at University Hospitals who works with the UH Roe Green Center for Travel Medicine & Global Health,tells Grow. "My advice would be to be vigilant, but calm, and not to panic."

To protect yourself from coronavirus, health professionals say the most important thing to do is wash your hands regularly. Don't forget to clean your phone regularly, too. "I clean my phone at least once a day," says Edwards. She advises others to do the same and many medical experts agree.

"It's often said that your phone is like a third hand because you're constantly touching it," says cleaning influencer Melissa Maker.

People take their phones out to eat, on the train, and to the bathroom. As a result, cellphones carry more than 17,000 bacterial gene copies each, according to a 2017 study. The report concluded that this "may play a role in the spread of infectious agents."

More from Grow:What to buy when your grocery store is out of pasta, beans, juiceHow a hairdresser plans to stretch her $4,000 savings while out of work3 smart ways to improve your finances while you're at home

Cleaning phones daily, at least, is smart, says Edwards."Certainly, if you are letting a lot of people use your phone, you would want to clean it to help prevent spread."

It's often said that your phone is like a third hand because you're constantly touching it.

Melissa Maker

Cleaning Influencer

If you want to clean your phone effectively, Maker says not to use a Lysolwipe or disinfectant wipe, as it may strip the coating of your phone over time. "The chemicals that are used in those disinfectant wipes are not meant to be used on electronics," she says.

Until recently, Apple advised against the use oftraditional cleaning products or compressed air.But earlier this month, Apple updated its instructions to say you can clean your phone with disinfectant wipes, as long as you wipe gently and avoid getting any liquid in charging ports.

GuidelinesforAndroidhandsets still advise steering clear of disinfectant wipes.

One alternative: Cleaning wipes that are specifically made for electronic devices. A 210-pack of individually wrapped lens- and screen-cleaning wipes is $16.99 on Amazon right now.

Maker suggests using a microfiber cloth. "Microfiber has the ability to pick up bacteria," Makers says. "Then you can launder the microfiber cloth."A six-pack of microfiber cleaning clothes is $9.99 on Amazon right now.

A damp microfiber cloth can remove microorganisms including viruses and bacteria and is more effective than a cotton rag, microbiologist Kristen Gibson told the The Wall Street Journal. It won't damage your phone the way a Lysol wipe might, either.

You can also pair onewith a homemade cleaner that is equal parts water and rubbing alcohol. Dip the cloth in the mixture, make sure it's not excessively wet, and then wipe down all parts ofyour phone. This will serve as an effective disinfectant.

And, of course, make sure you frequently wash your hands.

The article Clean Your Phone At Least Once a Day, Says Infectious Disease Specialist originally appeared on Grow by Acorns + CNBC.

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Clean your phone 'at least once a day,' medical experts say. Here's howwithout damaging the screen - CNBC

By GENE ESPYStaff WriterI cant tell you what a blessing it is, Mrs. Carolyn Parker Wooten said about her medical mission trips.Every place I have been I have left a piece of my heart and I can barely speak about it without choking up and tears coming to my eyes because I see these people living in squalor and they have basically nothing except a cellphone and a television. I went to be a blessing to these people, but I was the one who received the blessing.Carolyn Wooten was born and raised in Trion and graduated at Trion High School a River Rat as she explained.I walked across the street to school every day, Mrs. Wooten said.When she graduated at THS, she went into nursing school and is a Registered Nurse with a Bachelors Degree in Nursing.When she first began her career, medical missions had not come into play yet.Years later, after she had raised her family, a missionary came to the church she and her husband were attending for a mission conference. He was planning a trip to Peru and he said he really needed medical people to with him.It was like God reached out and touched my shoulder and said, He was talking to you.On our way home, I looked over to my husband and I said I have something to tell you, and he said, You want to go to Peru dont you? Mrs. Wooten continued.It was like he already knew, she added.I said, yes, I do, Wooten answered.She didnt know anything about Peru except it was something she felt like she needed to do.Mrs. Wooten met with the missionary and he explained what they did they go into the country as tourists, under the guidance and under the umbrella of a local church with a local pastor.What the Medical Missions does is follow the outline of Matthew 25:31-36.The purpose is to go reach people for their physical needs in order to meet their spiritual needs, Mrs. Wooten explained. I cant tell you what a blessing it is. I went to be a blessing to these people, but I was the one who received the blessing.As a registered nurse, she is recognized in other countries as being a medical provider under the guidance of the team that she is with. They have one doctor and have nurses that are providers.We dont just need medical people, we need people who are willing to give of their time to help set up the clinics, to help rebuild a wall that falls down because most of the countries they go to are Third World countries, Mrs. Wooten said.She said one of the things that she finds in these countries is not brushing your teeth for a week with tap water and using bottled water.When you get in the shower they tell you to be sure to keep your mouth tightly closed and your head down so the water doesnt get up your nose just because of the things that are in that water our bodies are not used to, she continued. I grew up on Trion water and we drank that straight out of the ground.

GUYANAOn the recent trip the group went to Guyana, South America with the Truth for Today Medical Missions.When you think about Guyana, you think about Jim Jones, she added. The people there have not forgotten what happened. There is a lot of gang activity and the worst thing a gang member can call another is a Jonesy Boy.Her group was a small group, they went to five separate areas, doing five clinics in five days.That was a lot of work, you have to set up everything and at the end of the day you take it all down and this involves moving church pews.Most of the clinics were in churches which are metal roofs over cinder block walls and then some very hard seats.The week they were there they saw 90 patients the first day; the second day they saw 69 medical and vision saw 80; the third day they saw 51 medical and 54 in vision; the next day they saw 90 in medical and 125 in vision and the last day they saw 96 in medical and 74 in vision.In the medical area the patients would come in and see Mrs. Wooten or one of the other providers and they would sit down and talk.I would ask, What can I do for you today? What kind of problems are you having? she continued.Most of them are joint pain, back pain and what they call the flu, which is sinus or upper respiratory and we treat them accordingly.They also did a lot of teaching about high blood pressure and diabetes which they have a lot of because of their high carbohydrates diets.We make sure that we get them started on medication so they can continue their medication through their socialized medicine, which is a disaster, Wooten added.Vision is a very big part of the clinics. She said that the Rotary boxes of old gasses, many times end up on a mission trip and many glasses you think are trash or you dont need them anymore, to these people the eyeglasses are a treasure.A billboard the group saw advertised financing for eyeglasses from six months up to two years.To give those people a pair of glasses, they have a machine called a refractor, they check their eyes and go through all the charts and then they know the strengths needed. They then go through the boxes of hundreds and hundreds of glasses and find the strength they need.The look on these peoples faces when they put on their glasses for the first time, they can see and they can read now, Mrs. Wooten said.There is no charge to the patients for the medical or the eyeglasses.Everything is either volunteer or free.She explained that the worst case she saw was a 17-year-old boy who was six foot, eight, and he was very thin. He was educated and still in school, and he was complaining about everything that was textbook for a bad thyroid. He had a goiter and for someone that young that is something that is not a good outcome.Rarely did we see someone that smoked, Mrs. Wooten added.I bring away from my trips how rich, how blessed and how fortunate we are to live in America, Mrs. Wooten said. And to be free and to have the freedoms that we have.

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Wooten's Medical Mission Trip To Guyana: 'I Have Been The One Blessed' Not Patients - Thesummervillenews

Newswise What gets the leader of the NIH jazzed?

Speaking to a packed West Pavilion auditorium March 6, Francis Collins, M.D., Ph.D., director of the National Institutes of Health, shared his picks of 10 areas of particular excitement and promise in biomedical research. (Watch the full talk here.)

In nearly every area, UAB scientists are helping to lead the way as Collins himself noted in several cases. At the conclusion of his talk, Collins addedhis advice for young scientists. Here is Collins top 10 list, annotated with some of the UAB work ongoing in each area and ways that faculty, staff and students can get involved.

1. Single-cell sequencing

[see this section of the talk here]

I am so jazzed with what has become possible with the ability to study single cells and see what they are doing, Collins said. They have been out of our reach now we have reached in. Whether you are studying rheumatoid arthritis, diabetes or the brain, you have the chance to ask each cell what it is doing.

Single-cell sequencing and UAB:Collins noted that Robert Carter, M.D., the acting director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, was a longtime faculty member at UAB (serving as director of the Division of Clinical Immunology and Rheumatology). For the past several years, UAB researchers have been studying gene expression in subpopulations of immune cells inpatients with rheumatoid arthritis.

Join in:Researchers can take advantage of the single-cell sequencing core facility in UABsComprehensive Flow Cytometry Core, directed by John Mountz, M.D., Ph.D., Goodwin-Blackburn Research Chair in Immunology and professor in the Department of Medicine Division of Clinical Immunology and Rheumatology.

Learn more:Mountz and other heavy users of single-cell sequencing explain how the techniqueslet them travel back in time and morein this UAB Reporter story.

2. New ways to see the brain

[See this section of the talk here]

The NIHsBRAIN Initiativeis making this the era where we are going to figure out how the brain works all 86 billion neurons between your ears, Collins said. The linchpin of this advance will be the development of tools to identify new brain cell types and circuits that will improve diagnosis, treatment and prevention of autism, schizophrenia, Parkinsons and other neurological conditions, he said.

Brain tech and UAB:Collins highlighted thework of BRAIN Initiative granteeHarrison Walker, M.D., an associate professor in the Department of Neurology, whose lab has been developing a more sophisticated way to understand the benefits of deep brain stimulation for people with Parkinsons and maybe other conditions, Collins said.

Join in:UABs planned new doctoral program in neuroengineering would be the first of its kind in the country.

Learn more:Find out why neuroengineering is asmart career choicein this UAB Reporter story.

3. Induced pluripotent stem (iPS) cells

[See this section of the talk here]

Researchers can now take a blood cell or skin cell and, by adding four magic genes, Collins explained, induce the cells to become stem cells. These induced pluripotent stem (iPS) cells can then in turn be differentiated into any number of different cell types, including nerve cells, heart muscle cells or pancreatic beta cells. The NIH has invested in technology to put iPS-derived cells on specialized tissue chips. Youve got you on a chip, Collins explained. Some of us dream of a day where this might be the best way to figure out whether a drug intervention is going to work for you or youre going to be one of those people that has a bad consequence.

iPS cells at UAB:Collins displayed images of thecutting-edge cardiac tissue chipdeveloped by a UAB team led by Palaniappan Sethu, Ph.D., an associate professor in the Department of Biomedical Engineering and the Division of Cardiovascular Disease. The work allows the development of cardiomyocytes that can be used to study heart failure and other conditions, Collins said.

Join in:UABs biomedical engineering department, one of the leading recipients of NIH funding nationally, is a joint department of the School of Engineering and School of Medicine. Learn more about UABsundergraduate and graduate programs in biomedical engineering, and potential careers, here.

Learn more:See howthis novel bioprinterdeveloped by UAB biomedical researchers is speeding up tissue engineering in this story from UAB News.

4. Microbiome advances

[See this section of the talk here]

We have kind of ignored the fact that we have all these microbes living on us and in us until fairly recently, Collins said. But now it is clear that we are not an organism we are a superorganism formed with the trillions of microbes present in and on our bodies, he said. This microbiome plays a significant role not just in skin and intestinal diseases but much more broadly.

Microbiome at UAB:Collins explained that work led by Casey Morrow, Ph.D., and Casey Weaver, M.D., co-directors of theMicrobiome/Gnotobiotics Shared Facility, has revealed intriguing information abouthow antibiotics affect the gut microbiome. Their approach has potential implications for understanding, preserving and improving health, Collins said.

Join in:Several ongoing clinical trials at UAB are studying the microbiome, including a studymodifying diet to improve gut microbiotaand an investigation of the microbiomes ofpostmenopausal women looking for outcomes and response to estrogen therapy.

Learn more:This UAB News storyexplains the UAB researchthat Collins highlighted.

5. Influenza vaccines

[See this section of the talk here]

Another deadly influenza outbreak is likely in the future, Collins said. What we need is not an influenza vaccine that you have to redesign every year, but something that would actually block influenza viruses, he said. Is that even possible? It just might be.

Influenza research at UAB:Were probably at least a decade away from a universal influenza vaccine. But work ongoing at UAB in the NIH-fundedAntiviral Drug Discovery and Development Center(AD3C), led by Distinguished Professor Richard Whitley, M.D., is focused on such an influenza breakthrough.

Join in:For now, the most important thing you can do to stop the flu is to get a flu vaccination. Employees can schedule afree flu vaccination here.

Learn more:Why get the flu shot? What is it like? How can you disinfect your home after the flu? Get all the information atthis comprehensive sitefrom UAB News.

6. Addiction prevention and treatment of pain

[See this section of the talk here]

The NIH has a role to play in tackling the crisis of opioid addiction and deaths, Collins said. The NIHs Helping to End Addiction Long-term (HEAL) initiative is an all-hands-on-deck effort, he said, involving almost every NIH institute and center, with the goal of uncovering new targets for preventing addiction and improving pain treatment by developing non-addictive pain medicines.

Addiction prevention at UAB:A big part of this initiative involves education to help professionals and the public understand what to do, Collins said. The NIH Centers of Excellence in Pain Education (CoEPE), including one at UAB, are hubs for the development, evaluation and distribution of pain-management curriculum resources to enhance pain education for health care professionals.

Join in:Find out how to tell if you or a loved one has a substance or alcohol use problem, connect with classes and resources or schedule an individualized assessment and treatment through theUAB Medicine Addiction Recovery Program.

Learn more:Discover some of the many ways that UAB faculty and staff aremaking an impact on the opioid crisisin this story from UAB News.

7. Cancer Immunotherapy

[See this section of the talk here]

We are all pretty darn jazzed about whats happened in the past few years in terms of developing a new modality for treating cancer we had surgery, we had radiation, we had chemotherapy, but now weve got immunotherapy, Collins said.

Educating immune system cells to go after cancer in therapies such as CAR-T cell therapy is the hottest science in cancer, he said. I would argue this is a really exciting moment where the oncologists and the immunologists together are doing amazing things.

Immunotherapy at UAB:I had to say something about immunology since Im at UAB given that Max Cooper, whojust got the Lasker Awardfor [his] B and T cell discoveries, was here, Collins said. This is a place I would hope where lots of interesting ideas are going to continue to emerge.

Join in:The ONeal Comprehensive Cancer Center at UAB is participating in a number of clinical trials of immunotherapies.Search the latest trials at the Cancer Centerhere.

Learn more:Luciano Costa, M.D., Ph.D., medical director of clinical trials at the ONeal Cancer Center, discusses the promise ofCAR-T cell therapy in this UAB MedCast podcast.

Assistant Professor Ben Larimer, Ph.D., is pursuing a new kind of PET imaging test that could give clinicians afast, accurate picture of whether immunotherapy is workingfor a patient in this UAB Reporter article.

8. Tapping the potential of precision medicine

[See this section of the talk here]

The All of Us Research Program from NIH aims to enroll a million Americans to move away from the one-size-fits-all approach to medicine and really understand individual differences, Collins said. The program, which launched in 2018 and is already one-third of the way to its enrollment goal, has a prevention rather than a disease treatment approach; it is collecting information on environmental exposures, health practices, diet, exercise and more, in addition to genetics, from those participants.

All of Us at UAB:UAB has been doing a fantastic job of enrolling participants, Collins noted. In fact, the Southern Network of the All of Us Research Program, led by UAB, has consistently been at the top in terms of nationwide enrollment, as School of Medicine Dean Selwyn Vickers, M.D., noted in introducing Collins.

Join in:Sign up forAll of Usat UAB today.

Learn more:UABs success in enrolling participants has led to anew pilot study aimed at increasing participant retention rates.

9. Rare diseases

[See this section of the talk here]

Rare Disease Day, on Feb. 29, brought together hundreds of rare disease research advocates at the NIH, Collins said. NIH needs to play a special role because many diseases are so rare that pharmaceutical companies will not focus on them, he said. We need to find answers that are scalable, so you dont have to come up with a strategy for all 6,500 rare diseases.

Rare diseases at UAB: The Undiagnosed Diseases Network, which includes aUAB siteled by Chief Genomics Officer Bruce Korf, M.D., Ph.D., is a national network that brings together experts in a wide range of conditions to help patients, Collins said.

Participants in theAlabama Genomic Health Initiative, also led by Korf, donate a small blood sample that is tested for the presence of specific genetic variants. Individuals with indications of genetic disease receive whole-genome sequencing. Collins noted that lessons from the AGHI helped guide development of the All of Us Research Program.

Collins also credited UABs Tim Townes, Ph.D., professor emeritus in the Department of Biochemistry and Molecular Genetics, for developing the most significantly accurate model of sickle cell disease in a mouse which has been a great service to the [research] community. UAB is now participating in anexciting clinical trial of a gene-editing technique to treat sickle cellalong with other new targeted therapies for the devastating blood disease.

Join in:In addition to UABs Undiagnosed Diseases Program (which requires a physician referral) and the AGHI, patients and providers can contact theUAB Precision Medicine Institute, led by Director Matt Might, Ph.D. The institute develops precisely targeted treatments based on a patients unique genetic makeup.

Learn more:Discover how UAB experts solved medical puzzles for patients by uncovering anever-before-described mutationandcracking a vomiting mysteryin these UAB News stories.

10. Diversity in the scientific workforce

[See this section of the talk here]

We know that science, like everything else, is more productive when teams are diverse than if they are all looking the same, Collins said. My number one priority as NIH director is to be sure we are doing everything we can to nurture and encourage the best and brightest to join this effort.

Research diversity at UAB:TheNeuroscience Roadmap Scholars Programat UAB, supported by an NIH R25 grant, is designed to enhance engagement and retention of under-represented graduate trainees in the neuroscience workforce. This is one of several UAB initiatives to increased under-represented groups and celebrate diversity. These include several programs from theMinority Health and Health Disparities Research Centerthat support minority students from the undergraduate level to postdocs; thePartnership Research Summer Training Program, which provides undergraduates and especially minority students with the opportunity to work in UAB cancer research labs; theDeans Excellence Award in Diversityin the School of Medicine; and the newly announcedUnderrepresented in Medicine Senior Scholarship Programfor fourth-year medical students.

Join in:The Roadmap program engages career coaches and peer-to-peer mentors to support scholars. To volunteer your expertise, contact Madison Bamman atmdbamman@uab.eduorvisit the program site.

Learn more:Farah Lubin, Ph.D., associate professor in the Department of Neurobiology and co-director of the Roadmap Scholars Program,shares the words and deeds that can save science careersin this Reporter story. In another story, Upender Manne, Ph.D., professor in the Department of Pathology and a senior scientist in the ONeal Comprehensive Cancer Center, explains how students in the Partnership Research Summer Training Program gethooked on cancer research.

Read the rest here:
Looking to the future with Dr. Francis Collins - Newswise

It's a startling number. Every 65 seconds in the U.S., someone develops Alzheimer's disease.

According to new research, there's a biological reason why women are more likely to get the disease.

Harry and Bettie Dunn love to reminisce about their past adventures during their 70 years of marriage.

"I know as you grow older you begin to lose some memory, but I noticed she was losing it more than I was," Harry said.

Harry believes it progressed more rapidly after a bad fall that broke Bettie's hip.

"She really doesn't know people that we've been friends with, sometimes she doesn't know her own children," he said.

"Two-thirds of Alzheimer's patients here in the U.S. are women," said Dr. Sepi Shokouhi, assistant professor of psychiatric and behavioral sciences at Vanderbilt University Medical Center.

Researchers examined 400 brain scans of elderly patients to figure out why the risk for Alzheimer's is higher for women than it is for men. They believe it may have something to do with an abnormal protein in the brain, named tau, which is linked to cognitive impairment.

"These abnormal proteins can spread like infection in the brain," Shokouhi said.

In the study, they found the tau accumulation was more widespread in women's brains than men's, easily moving from one part of the brain to another.

Previous theories on why more women got Alzheimer's disease than men pointed to the fact that women had a longer life expectancy. However, this research also points to a biological reason.

"I can predict that sex will be more strongly integrated in future precision medicine in Alzheimer's disease," Shokouhi said.

The new findings will help to identify therapies that would work best for women.

A study out of University of California at Los Angeles also points to social sex differences when it comes to Alzheimer's disease. They found the rate of memory decline was faster among married women who did not work in the labor force compared to married mothers who did.

Other researchers are studying possible causes like estrogen and one copy of a certain gene.

RESEARCH SUMMARYALZHEIMER'S ATTACKS MORE WOMEN THAN MEN REPORT #2717

BACKGROUND: Nearly 500,000 new cases of Alzheimer's disease will be diagnosed this year in the United States, and every 3 seconds, someone in the world develops dementia. Alzheimer's is the sixth-leading cause of death across all ages in the United States with a 5% increase in number of deaths in the from 2015 to 2016. For those 65 and older, it is the fifth-leading cause of death. Alzheimer's is an irreversible degeneration of the brain that causes disruptions in memory, cognition, personality, and other functions that eventually lead to death from complete brain failure. Caring for a person with Alzheimer's or another dementia is often extremely difficult, and many family and other unpaid caregivers experience high levels of emotional stress and depression as a result. (Source: https://www.brightfocus.org/alzheimers/article/alzheimers-disease-facts-figures)

ALZHEIMER AND GENDER: At the age of 65, women have a 1 in 5 chance of developing Alzheimer's, compared to a 1 in 11 chance for men. And, women in their 60's are twice as likely to develop Alzheimer's than to develop breast cancer. The Alzheimer's Association brought 15 of the world's leading scientists together to look further into why Alzheimer's is more likely in women, stating that "researchers are now questioning whether the risk of Alzheimer's could actually be higher for women at any given age due to biological or genetic variations or differences in life experiences." Genetic studies have offered a surprising account for the difference. Researchers from Stanford University studied over 8,000 people looking for a form of the gene ApoE-4, which increases the risk of Alzheimer's. They found that women who carry one copy of that gene variant were twice as likely to develop the disease as women without the gene. It is not clear why the gene poses such a drastic increase in risk but may be how the gene interacts with estrogen. (Source: https://www.alzheimers.net/8-12-15-why-is-alzheimers-more-likely-in-women/)

HOPEFUL BREAKTHROUGH: A study of more than 11,000 patients found that technology can detect biological evidence of brain changes clearly linked to Alzheimer's. The study involved people enrolled by nearly 1,000 dementia specialists across the country, and all had been diagnosed with either mildly impaired thinking skills or dementia in the last 2 years. "As in any other field of medicine, a clinical history and a physical exam is very important but being able to directly visualize the biology of the organ involved in the disease process is really essential to make an accurate diagnose," says lead study author Gil Rabinovici, MD, a professor at the University of California, San Francisco's Memory and Aging Center. This study used amyloid positron emission tomography, or PET scans, to detect amyloid plaques in the brain, which all people with Alzheimer's have. Before study participants were scanned, Alzheimer's disease was the leading cause suspected for cognitive impairment in 76.9% of patients, while the PET scans read as positive only for Alzheimer's in 55.3% of patients with mildly impaired thinking skills, and 70.1% of those with dementia. "Our hope is when we complete the second phase of the study, we will be able to show the scan not only changes management but improves outcomes, and that will lead Medicare to reconsider covering scans at least in some situations," Rabinovici says. (Source: https://www.webmd.com/alzheimers/news/20190501/alzheimers-diagnosis-breakthrough-hopeful-expensive)

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Alzheimer's attacks more women than men - WNDU-TV