AI that Can Shoot Down Fighter Planes Helps Treat Bipolar Disorder – Laboratory Equipment

The artificial intelligence that can blow human pilots out of the sky in air-to-air combat accurately predicted treatment outcomes for bipolar disorder, according to a new medical study by the University of Cincinnati. The findings open a world of possibility for using AI, or machine learning, to treat disease, researchers said. David Fleck, an associate professor at the UC College of Medicine, and his co-authors used artificial intelligence called genetic fuzzy trees to predict how bipolar patients would respond to lithium. Bipolar disorder, depicted in the TV show Homeland and the Oscar-winning Silver Linings Playbook, affects as many as 6 million adults in the United States or four percent of the adult population in a given year. In psychiatry, treatment of bipolar disorder is as much an art as a science, Fleck said. Patients are fluctuating between periods of mania and depression. Treatments will change during those periods. Its really difficult to treat them appropriately during stages of the illness.

The study authors found that even the best of eight common models used in treating bipolar disorder predicted who would respond to lithium treatment with 75 percent accuracy. By comparison, the model UC researchers developed using AI predicted how patients would respond to lithium 100 percent of the time. Even more impressively, the UC model predicted the actual reduction in manic symptoms after lithium treatment with 92 percent accuracy. The study authors found that even the best of the eight most common treatments was only effective half the time. But the model UC researchers developed using AI predicted how patients would respond to lithium treatment with 88 percent accuracy and 80 percent accuracy in validation. It turns out that the same kind of artificial intelligence that outmaneuvered Air Force pilots last year in simulation after simulation at Wright-Patterson Air Force Base is equally adept at making beneficial decisions that can help doctors treat disease. The findings were published this month in the journal Bipolar Disorders. What this shows is that an effort funded for aerospace is a game-changer for the field of medicine. And that is awesome, said Kelly Cohen, a professor in UCs College of Engineering and Applied Science. Cohens doctoral graduate Nicholas Ernest is founder of the company Psibernetix, Inc., an artificial intelligence development and consultation company. Psibernetix is working on applications such as air-to-air combat, cybersecurity and predictive analytics. Ernests fuzzy logic algorithm is able to sort vast possibilities to arrive at the best choices in literally the blink of an eye. Normally the problems our AIs solve have many, many googolplexes of possible solutions effectively infinite, study co-author Ernest said.

His team developed a genetic fuzzy logic called Alpha capable of shooting down human pilots in simulations, even when the computers aircraft intentionally was handicapped with a slower top speed and less nimble flight characteristics. The systems autonomous real-time decision-making shot down retired U.S. Air Force Col. Gene Lee in every engagement. It seemed to be aware of my intentions and reacting instantly to my changes in flight and my missile deployment, Lee said last year. It knew how to defeat the shot I was taking. It moved instantly between defensive and offensive actions as needed.

The American Institute of Aeronautics and Astronautics honored Cohen and Ernest this year for their advancement and application of artificial intelligence to large scale, meaningful and challenging aerospace-related problems. Cohen spent much of his career working with fuzzy-logic based AI in drones. He used a sabbatical from the engineering college to approach the UC College of Medicine with an idea: What if they could apply the amazing predictive power of fuzzy logic to a particularly nettlesome medical problem? Medicine and avionics have little in common. But each entails an ordered process a vast decision tree to arrive at the best choices. Fuzzy logic is a system that relies not on specific definitions but generalizations to compensate for uncertainty or statistical noise. This artificial intelligence is called genetic fuzzy because it constantly refines its answer, tossing out the lesser choices in a way analogous to the genetic processes of Darwinian natural selection. Cohen compares it to teaching a child how to recognize a chair. After seeing just a few examples, any child can identify the object people sit in as a chair, regardless of its shape, size or color. We do not require a large statistical database to learn. We figure things out. We do something similar to emulate that with fuzzy logic, Cohen said.

Cohen found a receptive audience in Fleck, who was working with UCs former Center for Imaging Research. After all, who better to tackle one of medical sciences hardest problems than a rocket scientist? Cohen, an aerospace engineer, felt up to the task. Ernest said people should not conflate the technology with its applications. The algorithm he developed is not a sentient being like the villains in the Terminator movie franchise but merely a tool, he said, albeit a powerful one with seemingly endless applications. I get emails and comments every week from would-be John Connors out there who think this will lead to the end of the world, Ernest said. Ernests company created EVE, a genetic fuzzy AI that specializes in the creation of other genetic fuzzy AIs. EVE came up with a predictive model for patient data called the LITHium Intelligent Agent or LITHIA for the bipolar study. This predictive model taps into the power of fuzzy logic to allow you to make a more informed decision, Ernest said. And unlike other types of AI, fuzzy logic can describe in simple language why it made its choices, he said. The researchers teamed up with Dr. Caleb Adler, the UC Department of Psychiatry and Behavioral Neuroscience vice chairman of clinical research, to examine bipolar disorder, a common, recurrent and often lifelong illness. Despite the prevalence of mood disorders, their causes are poorly understood, Adler said. Really, its a black box, Adler said. We diagnose someone with bipolar disorder. Thats a description of their symptoms. But that doesnt mean everyone has the same underlying causes. Selecting the appropriate treatment can be equally tricky. Over the past 15 years there has been an explosion of treatments for mania. We have more options. But we dont know who is going to respond to what, Adler said. If we could predict who would respond better to treatment, you would save time and consequences. With appropriate care, bipolar disorder is a manageable chronic illness for patients whose lives can return to normal, he said.

UCs new study, funded in part by a grant from the National Institute of Mental Health, identified 20 patients who were prescribed lithium for eight weeks to treat a manic episode. Fifteen of the 20 patients responded well to the treatment. The algorithm used an analysis of two types of patient brain scans, among other data, to predict with 100 percent accuracy which patients responded well and which didnt. And the algorithm also predicted the reductions in symptoms at eight weeks, an achievement made even more impressive by the fact that only objective biological data were used for prediction rather than subjective opinions from experienced physicians. This is a huge first step and ultimately something that will be very important to psychiatry and across medicine, Adler said. How much potential does this have to revolutionize medicine? I think its unlimited, Fleck said. Its a good result. The best way to validate it is to get a new cohort of individuals and apply their data to the system. Cohen is less reserved in his enthusiasm. He said the model could help personalize medicine to individual patients like never before, making health care both safer and more affordable. Fewer side-effects means fewer hospital visits, less secondary medication and better treatments. Now the UC researchers and Psibernetix are working on a new study applying fuzzy logic to diagnosing and treating concussions, another condition that has bedeviled doctors. The impact on society could be profound, Cohen said.

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AI that Can Shoot Down Fighter Planes Helps Treat Bipolar Disorder - Laboratory Equipment

Mammals May Have a 12-hour Clock – The Scientist


The Scientist
Mammals May Have a 12-hour Clock
The Scientist
Researchers led by Bert O'Malley of Baylor College of Medicine in Houston, Texas, identified a set of metabolism and stress genes in mouse liver cells that followed a pattern of expression on a 12-hour cyclestarting in the morning and again in the ...
A 12-hour biological clock coordinates essential bodily functionsEurekAlert (press release)

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Mammals May Have a 12-hour Clock - The Scientist

Hillsboro Native Earns Honors At Vanderbilt – thejournal-news.net

Hillsboro native Dr. Nancy J. Cox was honored this spring as the first recipient of the Richard M. Caprioli Research Award. Dr. Cox is currently the director of the Vanderbilt Genetics Institute in Nashville, TN.

The daughter of the late Gene and Helen Cox, she is a 1974 graduate of Hillsboro High School and was selected as the second Hillsboro Education Foundation Distinguished Alumni Award recipient in 2002.

Dr. Cox earned her bachelor of science degree in biology from the University of Notre Dame in 1978 and her doctorate in human genetics from Yale University in 1982.

She completed a postdoctoral fellowship in genetic epidemiology at Washington University and was a research associate in human genetics at the University of Pennsylvania.

In 1987, she was hired at the University of Chicago. She was appointed full professor in the departments of medicine and human genetics in 2004 and chief of the section of genetic medicine the following year.

In 2012, she was named a University of Chicago Pritzker Scholar. In 2015, Dr. Cox was hired at Vanderbilt University School of Medicine as the Mary Phillips Edmonds Gray Professor of Genetics, founding director of the Vanderbilt Genetics Institute and director of the Division of Genetic Medicine in the Department of Medicine. She is a fellow of the American Association for the Advancement of Science

Throughout her career as a quantitative geneticist, Dr. Cox has sought to identify and characterize the genetic component to common human diseases and clinical phenotypes like pharmacogenomics traits (how genes affect drug response).

Her work has advanced methods for analyzing genetic and genomic data from a wide range of complex traits and diseases, including breast cancer, diabetes, autism, schizophrenia, bipolar disorder, Tourette syndrome, obsessive-compulsive disorder, stuttering and speech and language impairment.

Through the national Genotype Tissue Expression (GTEx) project, Dr. Cox also contributed to the development of genome predictors of the expression of genes, and she also has investigated the genetics of cardiometabolic phenotypes such as lipids, diabetes and cardiovascular disease.

With colleagues at the University of Michigan, Dr. Cox is generating content for the Accelerating Medicine Partnership between the National Institutes of Health (NIH), U.S. Food and Drug Administration, biopharmaceutical companies and non-profit organizations. The goal of the partnership is to identify and validate promising biological targets, increase the number of new diagnostics and therapies for patients, and reduce the cost and time it takes to develop them.

Dr. Cox is co-principal investigator of an analytic center within the Centers for Common Disease Genomics, another NIH initiative that is using genome sequencing to explore the genomic contributions to common diseases such as heart disease, diabetes, stroke and autism. A major resource for the Cox lab is Vanderbilts massive biobank, BioVU, which contains DNA samples from more than 230,000 individuals that are linked to de-identified electronic health records.

Dr. Cox is the author or co-author of more than 300 peer-reviewed scientific articles. She is former editor-in-chief of the journal Genetic Epidemiology, and is the current president of the American Society of Human Genetics.

For developing new methods that have aided researchers worldwide in identifying and characterizing of the genetic and genomic underpinnings of diseases and complex traits, Dr. Cox is the first recipient of the inaugural Richard M. Caprioli Research Award.

Dr. Cox and her husband, Dr. Paul Epstein live in Nashville, TN, and have two grown daughters, Bonnie Epstein and Carrie Epstein.

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Hillsboro Native Earns Honors At Vanderbilt - thejournal-news.net

Mutations in CWC27 result in spectrum of conditions – Baylor College of Medicine News (press release)

An international team of researchers has discovered that mutations in the human gene CWC27 result in a spectrum of clinical conditions that include retinal degeneration and problems with craniofacial and skeletal development. The results appear in the American Journal of Human Genetics.

CWC27 is a new disease-associated gene, said co-senior author Dr. Rui Chen, associate professor of molecular and human genetics at Baylor College of Medicine.

One of the goals of the Chen lab is to identify genes involved with human retinal disease, such as retinitis pigmentosa, a condition characterized by progressive development of night blindness and tunnel vision, sometimes from the early age of 2. Retinitis pigmentosa is the most common inherited disorder of the retina; it affects nearly 1 in 4,000 people, and more than 1 million are visually impaired around the world due to this untreatable disease.

In our search for genes linked to retinitis pigmentosa, we identified a patient with the condition more than two years ago, said co-first author Mingchu Xu, graduate student in molecular and human genetics in the Chen lab. We identified a frameshift mutation in CWC27. The patient did not have other conditions in addition to the vision problems. To study the condition, we mimicked the human mutation in a mouse model, and at 6 months of age the mice showed retinal degeneration and no other conditions, just as we had observed in the human patient.

CWC27 is one of more than 100 genes that participate in the formation and function of the spliceosome, a molecular machine that is involved in the correct expression of the proteins that carry out the functions of all the cells in the body. Until now, most disease-associated genes of the spliceosome had been involved in two non-overlapping conditions. For instance, mutations in certain proteins of the spliceosome cause syndromes that involve mainly craniofacial and skeletal conditions, while mutations in other spliceosome genes result only in retinitis pigmentosa. CWC27 seemed to belong to the second group of genes.

Surprising results

Interestingly, our collaborator Dr. Daniel Schorderet, director of the Institute for Research in Ophthalmology in Switzerland and co-senior author of the paper, was working with patients who have mutations in CWC27 and present with more severe clinical conditions than our patient, including craniofacial and skeletal problems in addition to problems with vision, Xu said.

When we looked at the clinical characteristics of all the patients, we did not anticipate that they would have mutations in the same gene. Only when we looked at the genes did we realize that the spectrum of clinical characteristic in the patients was the result of various mutations in the same gene, CWC27, Chen said.

By applying exome sequencing to multiple families and modeling the disease in two mouse models the researchers were able to appreciate the spectrum of clinical conditions that mutations in the same gene can cause.

This is the first time a mutation of a gene in the spliceosome has been described to result in an entire spectrum of clinical conditions, Xu said. To explain why our patient presented only with vision problems, we hypothesized that the mutation in our patients CWC27 was milder than those of other patients. By analyzing the results on mouse models and patient samples, we found that the mutant gene in our patient probably retains a residual function, while the genes in the patients of the other groups have a more severe loss of function.

This study also shows the power of collaboration within the genetics community when looking for new disease-associated genes, Xu said. Initially, we only identified one patient and then we collected more cases via two platforms, GeneMatcher and the European Retinal Disease Consortium. We would not have been able to present this interesting story without the contributions of researchers from nine countries. With exome sequencing accessible to more patients and researchers, these platforms will most likely speed up the process of finding the genetic causes of human diseases.

Seea complete list of authors and their affiliations and the financial support for this project.

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Mutations in CWC27 result in spectrum of conditions - Baylor College of Medicine News (press release)

Study: Gene Test Needed Before Using Alzheimer’s Drug ‘Off-Label’ – Montana Standard

TUESDAY, March 7, 2017 (HealthDay News) -- A drug used to treat Alzheimer's disease should not be prescribed to people with milder mental impairment without first giving them a genetic test, a new study urges.

The drug is donepezil (brand name: Aricept).

Donepezil could speed mental decline in someone with mild cognitive impairment who has a specific genetic variation, according to Sophie Sokolow, an associate professor at the UCLA School of Nursing.

She and her colleagues found that patients with the K-variant of the butyrylcholinesterase (BChE) gene who took donepezil deteriorated faster than those who took a placebo.

Donepezil is approved in the United States to treat Alzheimer's disease but not mild cognitive impairment -- the stage between normal age-related decline and dementia. However, doctors often prescribe it "off-label" for patients with mild cognitive impairment, the study authors said.

For this study, the researchers examined data from a U.S. government-funded study published in 2005 that assessed donepezil as a possible treatment for mild cognitive impairment.

The findings reinforce the importance of physicians discussing the possible benefits and risks of donepezil with their patients, the researchers said in a university news release.

The study was published recently in the Journal of Alzheimer's Disease. Funding was provide by the U.S. National Institute on Aging.

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Study: Gene Test Needed Before Using Alzheimer's Drug 'Off-Label' - Montana Standard

Intellia R&D head says new gene-editing data shows path to human trials – Boston Business Journal


Boston Business Journal
Intellia R&D head says new gene-editing data shows path to human trials
Boston Business Journal
Cambridge-based Intellia Therapeutics had the biggest IPO of any local biotech in 2016, but shares of the company have lagged in recent months, and it has often been overshadowed by its gene-editing rival in Kendall Square, Editas Medicine.

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Intellia R&D head says new gene-editing data shows path to human trials - Boston Business Journal

Study parses influence of genes and environment in metabolic disease – Medical Xpress

March 8, 2017 White fat stores energy, while brown fat dissipates energy by producing heat, mediated by uncoupling protein 1, or UCP1. Credit: Ray Soccio, MD, PhD, Perelman School of Medicine, University of Pennsylvania

By comparing two strains of miceone that becomes obese and diabetic on a high-fat diet and another resistant to a high-fat regimenresearchers from the Perelman School of Medicine at the University of Pennsylvania identified genome-wide changes caused by a high-fat diet.

The a team, led by Raymond Soccio, MD, PhD, an assistant professor of Medicine, and Mitchell Lazar, MD, PhD, director the Institute for Diabetes, Obesity, and Metabolism, published their findings online in the Journal of Clinical Investigation (JCI), in addition to an Author's Take video.

"We focused on the epigenome, the part of the genome that doesn't code for proteins but governs gene expression," Lazar said.

Their research suggests that people who may be genetically susceptible to obesity and type 2 diabetes due to low levels of a protein that helps cells burn fat, may benefit from treatments that ultimately increase the fat-burning molecule.

The team looked at the interplay of genes and environment in two types of white fat tissue, subcutaneous fat (under the skin) versus visceral fat around abdominal organs. The latter correlates strongly with metabolic disease. This visceral fat shows major gene expression changes in diet-induced obesity. The JCI study confirmed this relationshipand importantlyextended these findings to show that the epigenome in visceral fat also changes on a high fat diet.

Diet-induced epigenomic changes in fat cells occur at histones - proteins that package and order DNA in the nucleus, which influences gene expression - across the genome. There were also changes in the binding to DNA of an essential fat cell protein, a transcription factor called PPARgamma.

The team next treated obese mice with the drug rosiglitazone, which targets PPARgamma in fat to treat diabetes in people. "While the drug-treated obese mice were more insulin sensitive, we were surprised to see that the drug had little effect on gene expression in visceral fat," Soccio said. "This led us to look at subcutaneous fat and we discovered that this depot is much more responsive to the drug."

"These results are clinically relevant and indicate that the 'bad' metabolic effects of obesity occur in visceral fat, while the 'good' effects of rosiglitazone and other drugs like it occur in subcutaneous fat," Lazar said.

In particular, the drug-induced changes they found in subcutaneous fat reflected the phenomenon of browning, in which white fat takes on characteristics of brown fat, typically in response to cold exposure or certain hormones and drugs.

White fat stores energy, while brown fat dissipates energy by producing heat, mediated by uncoupling protein 1, or UCP1. The most interesting discovery of the study, say the authors, involves UCP1.

They showed that rosiglitazone, as expected, increases Ucp1 expression in both obesity-prone and obesity-resistant strains of mice. However, in subcutaneous fat of the obesity-resistant mice, Ucp1 expression was high even in the absence of the drug. "But the real surprise came when we looked at the offspring of obesity-resistant and obesity-prone parents, which have one of each parent's version of the Ucp1 gene," Soccio said.

Strikingly, they found that the obesity-prone mouse strain's version of the Ucp1 gene has lower expression and less PPARgamma binding than the obesity-resistant version. This imbalance shows that the obesity-prone mouse strain's Ucp1 is genetically defective, since it is less active than the other strain's version, even when both are present in the same cell nucleus.

In their final experiments, the team asked what happens when browning and Ucp1 expression are activated using rosiglitazone or exposure to cold, both environmental factors. They found that in both cases, total Ucp1 expression goes up as expected, but the obesity-prone strain's defective version of Ucp1 now reaches equal levels to the obesity-resistant strain's version.

"Importantly, we were only changing the mouse's environment with a drug or temperature, not the actual DNA sequence of the Ucp1 gene," Lazar said. "We propose that this result indicates epigenomic rescue of Ucp1 expression in subcutaneous fat cells."

The team is following up the mouse studies using human fat biopsies to figure out the exact DNA sequence differences responsible for variable Ucp1 expression, both in mice and in humans.

The relevance of this study extends even beyond UCP1 and obesity. "Many gene variants are thought to exert their effects by ultimately altering gene expression levels, and this study shows that a genetic predisposition to altered gene expression can be identified and then overcome with treatment," Lazar said. "This is the dream of precision medicine, and hopefully our study is a step in this direction."

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Study parses influence of genes and environment in metabolic disease - Medical Xpress

Genetic driver behind rare skeletal dysplasia condition found – Baylor College of Medicine News (press release)

Researchers in the Department of Molecular and Human Genetics at Baylor College of Medicine have identified a previously unimplicated gene behind a particular form of chondrodysplasia, a skeletal dysplasia that affects cartilage formation and causes disproportionate short stature and premature osteoarthritis. The study appears in the Journal of Clinical Investigation.

Stemming from research being performed at Baylor and its genetics department as part of a systematic search for genetic causes of skeletal dysplasias, the project set out to identify the genetic driver behind Shohat type spondyloepimetaphyseal dysplasia (SEMD). It was led by Dr. Brendan Lee, professor and chair of molecular and human genetics at Baylor, and a team of researchers including project leader Adetutu Egunsola, a genetics graduate student.

SEMD is a rare type of skeletal dysplasia that impacts the development of cartilage and results in a form of dwarfism, characterized by a particular pattern of joint abnormalities, scoliosis and defects of the long bones.

Through combined whole exome sequencing and studies in zebrafish and mice, Lee and his team were able to identify a completely new gene associated with this skeletal dysplasia, DDRGK1, and discovered how it functions in cartilage. In zebrafish, for example, a DDRGK1 deficiency disrupts craniofacial cartilage development and causes a decrease in levels of the protein SOX9.

Not only did we discover the requirement of DDRGK1 in maintaining cartilage, but we also found that it to be a regulator of SOX9, which is the master transcription factor that controls cartilage formation the human skeleton, said Lee, who also holds the Robert and Janice McNair Endowed Chair in molecular and human genetics. If you do not have the SOX9 protein, you do not have cartilage it drives the production of cartilage in growth plates and joint cartilage all over the body.

The relationship between DDRGK1 and SOX9 reveals a novel mechanism that regulates chondrogenesis, or cartilage maintenance and formation, by controlling SOX9 ubiquitination, a process that controls the degradation of proteins like SOX9. Loss of the function of DDRGK1 causes this cartilage dysplasia in part via accelerated destruction of SOX9.

Studying this skeletal dysplasia resulted in the biological insight about this gene that had never been implicated in any disease condition related to the skeleton, Lee said. The future is to find out whether DDRGK1s function more globally controls ubiquitination in general and to determine how this process could be targeted for treating patients with dwarfism.

Other contributors to this work include Richard Gibbs, Adetutu T. Egunsola, Yangjin Bae, Ming-Ming Jiang, David S. Liu, Yuqing Chen-Evenson, Terry Bertin, Shan Chen and James T. Lu with Baylor, Nurit Magal with Rabin Medical Center, Annick Raas-Rothschild with Sheba-Tel Hashomer Medical Center, Eric C. Swindell with the University of Texas Graduate School of Biomedical Sciences, Lisette Nevarez and Daniel H. Cohn with the University of California, Philippe M. Campeau with the University of Montreal and Mordechai Shohat with the Sackler School of Medicine at Tel Aviv University.

This research was supported by the BCM Intellectual and Developmental Disabilities Research Center and a Program Project grant from the Eunice and Kennedy Shiver National Institute of Child Health and Human Development, the BCM Advanced Technology Cores with funding from the NIH, the Rolanette and Berdon Lawrence Bone Disease Program of Texas, the BCM Center for Skeletal Medicine and Biology and Tel Aviv University.

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Genetic driver behind rare skeletal dysplasia condition found - Baylor College of Medicine News (press release)

Doctors reverse teen’s sickle cell disease with innovative gene therapy – Fox News

A French teen who underwent a first-of-its-kind procedure 15 months ago to change his DNA shows no signs of the sickle cell disease he had been suffering from. The procedure, which was performed at Necker Childrens Hospital in Paris, may offer hope to millions of patients who suffer from sickle cell disease, BBC News reported.

Sickle cell disease is a severe hereditary form of anemia, which causes patients to develop abnormal hemoglobin in red blood cells. The botched hemoglobin causes the cells to form a crescent or sickle shape, making it difficult to maneuver throughout the body. Sickle-shaped cells are less flexible, and may get stuck to vessel walls causing a blockage, which can stop blood flow to vital tissues.

Before undergoing the procedure, treatment for the unidentified teen included traveling to the hospital each month for a blood transfusion to dilute the defective blood, BBC News reported. According to the report, the excessive amount of treatment caused severe internal damage, and at age 13 he already needed a hip replacement and had his spleen removed.

In a world first, doctors at Necker Childrens Hospital removed his bone marrow and genetically altered it using a virus to compensate for the defect in his DNA responsible for sickle cell disease, BBC News reported. The results published in the New England Journal of Medicine said he no longer uses medication, and has been making normal blood for the past 15 months.

So far the patient has no sign of the disease, no pain, no hospitalization, Philippe Leboulch, professor of medicine at the University of Paris, told BBC News. He no longer requires a transfusion so we are quite pleased with that.

Doctors said the treatment will have to be repeated in other patients as the teen is the trials first, but that it does show powerful potential.

Ive worked in gene therapy for a long time and we make small steps and know theres years more work, Dr. Deborah Gill, of the gene medicine research group at the University of Oxford, told BBC News. But here you have someone who has received gene therapy and has complete clinical remission thats a huge step forward.

It was not clear how much the procedure would cost, or whether there are plans to expand to other countries.

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Sanford Health, hospital partner on gene sequencing project – Medical Xpress

March 3, 2017

Sanford Health, one of the largest health systems in the country, is partnering with the flagship hospital of the Miami Children's Health System to sequence the genes of nearly 1,000 Latinos and Hispanics in order to better understand the health needs of the populations.

Philanthropist Denny Sanford and Sanford Health have given $7 million to the Nicklaus Children's Hospital initiative in Miami, Florida, to support the research, which uses genetic and genomic information to personalize health carein this case, for children.

Golfing great Jack Nicklaus, for whom the hospital is named, said he recently approached his friend, Denny Sanford, and asked for help with the project.

"When we approached Denny with a plea to assist our important work at Nicklaus Children's Hospital and through our Foundation, he was quick to open his heart and lend a hand," Nicklaus said in a statement.

The sequencing project will make it easier to determine whether a person is predisposed to a certain disease, or how he or she might respond to a particular medicine. The initiative will help build a database of common genomes and identify genetic patterns among Hispanic and Latino populations.

MCHS is South Florida's only health care system exclusively for children and includes the nonprofit Nicklaus Children's Hospital.

Sanford Health, which is the largest employer based in the Dakotas with 28,000 workers, has 45 hospitals and nearly 300 clinics in nine states and four countries. Sanford Health CEO Kelby Krabbenhoft said the partnership will help Sanford diversify its work and research with genomic medicine.

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Icahn Names Gene Transfer Pioneer as Portfolio Manager – Genetic Engineering & Biotechnology News

Days after reportedly taking a stake in Bristol-Myers Squibb, Carl C. Icahn signaled an even greater role as an activist investor in biopharma through the hiring of Richard C. Mulligan, Ph.D., as a portfolio manager.

Dr. Mulligan will focus on biotechnology investments for two Icahn limited partnerships, Icahn Partners and Icahn Partners Master Fund, the private investment funds comprising Icahn Enterprises' Investment segment.

"We are very pleased to have Richard join Icahn Capital given the depth and level of experience he brings as we look to enhance our focus on the biotechnology sector," Icahn, the chairman of Icahn Enterprises, said in a statement earlier this week.

Dr. Mulligan is the Mallinckrodt Professor of Genetics, Emeritus at Harvard Medical School (HMS) and visiting scientist at the Koch Institute for Integrative Cancer Research at MIT. He is also a pioneer in the development of new technologies for transferring genes into mammalian cells. A major interest in Dr. Mulligan's laboratory has been the development of genetically engineered animal viruses as gene transfer vectors.

In addition to serving as full Mallinckrodt professor at HMS, he previously served as director of the Harvard Gene Therapy Initiative, a collaboration by basic science and clinical investigators at Harvard University and its affiliated hospitals focused on preclinical and clinical evaluation of novel gene-based therapies for inherited and acquired diseases.

From 2013 to last year, Dr. Mulligan was founding partner and senior managing director of Sarissa Capital Management. Sarissaled by another biopharma-focused activist investor, Alex Dennerspearheaded the successful effort in 2015 to drive Harvey J. Berger, M.D., into retirement from the helm of Ariad Pharmaceuticals, the cancer drug developer that he founded in 1991 and is being acquired by Takeda Pharmaceutical for $5.2 billion.

Dr. Mulligan is a member of Biogens board and has previously served as a director, scientific advisory board member, or officer for numerous public biopharma companies, including Cell Genesys, Cellectis, Enzon, Somatix Therapy, and ImClone. ImClone was acquired by Eli Lilly for $6.5 billion in 2008, 2 years after Icahn acquired a majority of the companys stock.

Dr. Mulligan was also a consultant to Amgen, DuPont, and the Genetics Institute. He previously served on the NIHs Recombinant DNA Advisory Committee, which provides guidance to the agency about experiments involving recombinant DNA, and the FDA Biological Response Modifiers Advisory Committee, which advises the FDA on matters related to cell and gene therapies, including stem cell-based technologies.

He received his B.S. degree from MIT and his Ph.D. from the department of biochemistry at Stanford University School of Medicine, where he studied under Nobel Laureate Paul Berg, Ph.D.

After receiving postdoctoral training at the Center for Cancer Research at MIT with Nobel Laureates David Baltimore, Ph.D., and Phillip Sharp, Ph.D., Dr. Mulligan joined the MIT faculty and was appointed Professor of Molecular Biology and Member of the Whitehead Institute for Biomedical Research before moving to Harvard and Children's Hospital in 1996.

His honors include the MacArthur Foundation "Genius" Prize, the Rhodes Memorial Award of the American Association for Cancer Research, the ASMB-Amgen Award, and the Nagai Foundation International Prize.

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Icahn Names Gene Transfer Pioneer as Portfolio Manager - Genetic Engineering & Biotechnology News

The Multitude of Issues Surrounding Human Embryo Gene Editing – Healthline

Should scientists be allowed to dive deep into an embryos DNA and dig out an inheritable disease?

Should parents be allowed to tweak an unborn childs genes to make their child tall or athletic or smart?

And what would be the consequences of all this on human evolution?

Those are some of the questions facing the medical community and society in general as limited experiments begin in the United States on human embryo gene editing.

An advisory group formed by the National Academy of Sciences and National Academy of Medicine recommended last month that this kind of research should begin.

However, the panel said it should only be done in rare cases where there is no alternative to preventing a baby from acquiring a serious disease or disability.

Read more: Scientists finding gene editing with CRISPR hard to resist

Research on editing the genes of human embryos is already underway in China and Sweden.

Clinical trials using gene editing to treat noninheritable conditions are already set to start in the United States.

However, editing out inheritable ones like Huntington disease, cystic fibrosis, or Alzheimers disease from the genes of human embryos is a bigger undertaking, both scientifically and ethically.

Such editing could eliminate the risk of the disease for the embryos as well as eliminate these conditions for any offspring the embryos might produce as an adult.

But experts say that germline editing could cause unintended, permanent effects on human evolution.

It also could open up the ability to edit embryos for enhanced physical or mental characteristics, creating so-called designer babies.

In the past year, new, cheaper technologies particularly the adoption of the more precise gene editing tool CRISPR-Cas9 have made it more likely researchers will actually succeed at editing human embryos.

That makes the debate over these concerns no longer hypothetical.

The technology could save millions of lives.

Or it could lead to an ever-growing divide between those who can afford to pay for enhanced medical treatments and those who cant.

Read more: CRISPR gene technology gets approval for cancer treatment

Lets say you and your partner both have cystic fibrosis with the same mutations.

But you want to have a child who doesnt have the disease.

Genetic editing could be the answer.

Such embryonic manipulation would involve a small number of couples with specific conditions and preferences and lack of alternatives.

But, as University of Manchester Bioethicist John Harris told National Geographic, if suffering and death can be averted by this research the decision to delay such research should not be made lightly. Just as justice delayed is justice denied, so, too, therapy delayed is therapy denied. That denial costs human lives, day after day.

For most couples, there would be other options available, points out Marcy Darnovsky, PhD, director of the Center for Genetics and Society in California.

Some might be able to use an egg or sperm donor or screen embryos with preimplantation genetic diagnosis in a fertility clinic.

There is also the question of what this research will mean not just for our health but for our perceptions of society.

If we can do away with a disease like cystic fibrosis, for instance, how will that affect how we view and treat those who still have it?

What will we be saying about who is healthy and who isnt?

Its a way of setting a bar about what kinds of people should be born, Darnovsky told Healthline. There are concerns about stigmatizing conditions and reducing the social supports of people who do live with those conditions.

Read more: Gene editing could be used to battle mosquito-borne diseases

All these implications are years or even decades away.

The research that will happen in the near term is more about improving the technology, not modifying embryos intended to be gestated and born.

That germline editing, in fact, is not allowed because of a prohibition on using federal funds to review research in which a human embryo is intentionally created or modified to include a heritable genetic modification.

In addition, the advisory panels report states that the technology is not ready for human trials.

But it also said using it to edit the precursors of humans embryos, eggs, sperm could soon be a realistic possibility that deserves serious consideration.

For now, someone who is interested in one day benefiting from embryo editing should undergo carrier testing to see if and how much they are at risk of passing on a heritable disease.

Go through your [doctor], not one of those companies where you send off your spit in a vial, said Darnovsky.

She said physicians have the time, training, and resources to make sure youre fully informed about any conditions or decisions youll have to make.

In addition, they can also keep you updated on new technologies and ethical quandaries as they emerge.

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The Multitude of Issues Surrounding Human Embryo Gene Editing - Healthline

Genetic variant linked to overactive inflammatory response – Science Daily

Researchers at Cardiff University have discovered that genetic variation is the reason why some immune systems overreact to viruses.

Previous research had already revealed that a gene called Ifitm3 influences how sensitive people are to the influenza virus, with a variant form of the gene making cells more susceptible to viral infection. The new research reveals that Ifitm3 also plays an important role in controlling the extent of the inflammatory response triggered by virus infection.

The study suggests that individuals with deficiencies in Ifitm3 may have an overactive immune response to viral infection and may therefore be helped by a combination of anti-inflammatory drugs in addition to medicine that directly targets the virus.

World-wide the frequency of the variant Ifitm3 gene is 1 in 400, although it is much more common in certain ethnicities.

Dr Ian Humphreys from Cardiff University's School of Medicine said: "Now we know that genetic make-up influences how the immune system copes with infections, not only by influencing how the body controls an infection but also by controlling how strongly the body's immune system reacts, we can design therapeutic strategies for individuals who are seriously ill with infections, which are tailored to the individual based on their genetic profile."

The data were collected using immune cells from mice with and without the variant form of Ifitm3, to observe how the immune system responds to a virus called cytomegalovirus. The results could also be relevant for other viral infections such as influenza epidemics/pandemics.

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Materials provided by Cardiff University. Note: Content may be edited for style and length.

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Genetic variant linked to overactive inflammatory response - Science Daily

Vaccines, Antibodies and Drug Libraries. The Possible COVID-19 Treatments Researchers Are Excited About – TIME

In early April, about four months after a new, highly infectious coronavirus was first identified in China, an international group of scientists reported encouraging results from a study of an experimental drug for treating the viral disease known as COVID-19.

It was a small study, reported in the New England Journal of Medicine, but showed that remdesivir, an unapproved drug that was originally developed to fight Ebola, helped 68% of patients with severe breathing problems due to COVID-19 to improve; 60% of those who relied on a ventilator to breathe and took the drug were able to wean themselves off the machines after 18 days.

Repurposing drugs designed to treat other diseases to now treat COVID-19 is one of the quickest ways to find a new therapy to control the current pandemic. Also in April, researchers at Vanderbilt University enrolled the first patients in a much-anticipated study of hydroxychloroquine. Its already approved to treat malaria and certain autoimmune disorders like rheumatoid arthritis and lupus but hasnt been studied, until now, against coronavirus. Yet the medication has become a sought-after COVID-19 treatment after first Chinese doctors, and then President Trump touted its potential in treating COVID-19. The data from China is promising but not conclusive, and infectious disease experts, including Trumps coronavirus task force scientific advisor Dr. Anthony Fauci, arent convinced its ready for prime time yet in Americas emergency rooms and intensive care units.

But doctors facing an increasing flood of patients say they dont have time to wait for definitive data. In a survey of 5,000 physicians in 30 countries conducted by health care data company Sermo, 44% prescribed hydroxychloroquine for their COVID-19 patients, and 38% believed it was helping. Such off-label use in using a drug approved to treat one disease to treat another is allowed, especially during a pandemic when no other therapies are available. A similar percentage said remdesivir was very or extremely effective in treating COVID-19. (Although remdesivir is not approved for treating any disease, the Food and Drug Administration granted special authorization for doctors to use it to treat the sickest COVID-19 patients.)

That explains the unprecedented speed with which the hydroxychloroquine studyand others like itare popping up around the world. There are no treatments proven to disable SARS-CoV-2, the virus that causes the disease, which means all the options scientists are exploring are still very much in the trial-and-error stage. Still, they are desperate for anything that might provide even a slim chance of helping their patients survive, which is why studies are now putting dozens of different therapies and a handful of vaccines to the test. The normal road to developing new drugs is often a long oneand one that frequently meanders into dead ends and costly mistakes with no guarantees of success. But given the speed at which SARS-CoV-2 is infecting new hosts on every continent across the globe, those trials are being ushered along at a breakneck pace, telescoping the normal development and testing time by as much as half.

The newly launched Vanderbilt study, led by the National Heart, Lung, and Blood Institute of the U.S. National Institutes of Health, will enroll more than 500 people who have been hospitalized with COVID-19 and randomly assign them to receive hydroxychloroquine or placebo. It would be the first definitive trial to test whether hydroxychloroquine should be part of standard therapy for treating COVID-19, and its lead scientist expects results in a few months.

The sense of urgency is pushing other researchers at academic institutes as well as pharmaceutical companies to turn to their libraries of thousands of approved drugs or compounds that are in early testing and screening to see if any can disable SARS-CoV-2. Because these are either already approved and deemed safe for people, if any emerge as possible anti-COVID-19 therapies, companies could begin testing them in people infected with the virus within weeks. Other teams are mining recovered patients blood for precious COVID-19-fighting immune cells, and because the virus seems to attack the respiratory system, scientists are also finding clever ways to stop it from compromising lung tissue.

These are all stop-gap measures, however, since ultimately, a vaccine against COVID-19 is the only way to arm the worlds population against new waves of infection. Established pharmaceutical powers like Johnson & Johnson, Sanofi and Glaxo SmithKline are racing shoulder-to-shoulder to with startups using new technology to develop dozens of potential new vaccines, with the hope of inoculating the first people next yearnone too soon before what public health officials anticipate might be another season of either the same, or potentially new, coronavirus.

We know these viruses reside in animal species, and surely another one will emerge, says Dr. David Ho, director of the Aaron Diamond AIDS Research Center and professor of medicine at Columbia University, who is heading an effort to screen antiviral drug compounds for new COVID-19 treatments. We need to find permanent solutions to treating them, and should not repeat the mistake that once an epidemic wanes, interest and political will and funding also wanes.

Its an old-school approach that dates back to the late 19th century, but the intuitive logic behind using plasma from recovered patientstechnically called convalescent plasmaas a treatment might still apply today. Plasma treatments have been used with some success to treat measles, mumps and influenza. The idea is to use immune cells extracted from the blood of people who have recovered from COVID-19 and infuse them into those who are infected, giving them passive immunity to the disease, which could at least minimize some of its more severe symptoms.

Its part of a broader range of tactics that utilize the bodys own immune response as a molecular North Star for charting the course toward new treatments. And by far, antibodies against the virus are the most abundant and efficient targets, so a number of pharmaceutical and biotechnology companies are concentrating on isolating the ones with the strongest chance of neutralizing SARS-CoV-2.

In late March, New York Blood Center became the first U.S. facility to start collecting blood from recovered COVID-19 patients specifically to treat other people with the disease. Doctors at New Yorks Mount Sinai Health System are now referring recovered (and willing) patients to the Blood Center, which collects and processes the plasma and provides the antibody-rich therapy back to hospitals to treat other COVID-19 patients.. Its not clear yet whether the practice will work to treat COVID-19, but the Food and Drug Administration (FDA) is allowing doctors to try the passive immunity treatment in the sickest patients on a case by case basis, as long as they apply for permission to use or study the plasma an investigational new drug. If we can passively transfuse antibodies into someone who is actively sick, they might temporarily help that person fight infection more effectively, so they can get well a little bit quicker, says Dr. Bruce Sachais, chief medical officer at New York Blood Center Enterprises.

The biggest drawback to this approach, however, is the limited supply of antibodies. Each recovered donor has different levels of antibodies that target SARS-CoV-2, so collecting enough can be a problem, especially if the need continues to surge during an ongoing pandemic. At the Maryland-based pharmaceutical company Emergent BioSolutions, scientists are trying to overcome this challenge by turning to a unique source of plasma donors: horses. Their size makes them ideal donors, says Laura Saward, head of the companys therapeutic business unit. Scientists already use plasma from horses to produce treatments for botulism (a bacterial infection), and have found that the volume of plasma the animals can donate means each unit can treat more than one patient (with human donors, at this point, one unit of plasma from a donor can treat one patient). Horses plasma may also have higher concentrations of antibody, so the thought is that a smaller dose of equine plasma would be effective in people because there would be higher levels of antibody in smaller doses, says Saward. By the end of the summer, the company expects its equine plasma to be ready for testing in people.

Scientists are also looking for other ways to generate the virus-fighting antibodies produced by COVID-19 patients. At Regeneron, a biotechnology firm based in New York, researchers are turning to mice bred with human-like immune systems and infected with SARS-CoV-2. Theyre searching hundreds of antibodies these animals produce for the ones that can most effectively neutralize the virus. By mid-April, the company plans to start manufacturing the most powerful candidates and prepare them (either solo or in combination) for human testingboth in those who are already infected, as well as in healthy people, to protect from getting infected in the first place, like a vaccine.

Its not just people and animals that can produce antibodies. Scientists now have the technology to build what are essentially molecular copying machines that can theoretically churn out large volumes of the antibodies found in recovered patients. At GigaGen, a San Francisco-based biotech startup founded by Stanford University professor Dr. Everett Meyer, scientists are identifying the right antibodies from recovered COVID-19 patients and hoping to use them as a template for synthesizing new ones, in a more consistent and efficient way so a handful of donors could potentially produce enough antibodies to treat millions of patients. What GigaGens technology does is almost Xerox copy a big swath of the human repertoire of antibodies, and then takes those copies and grows it in cells [in the lab] to manufacture more antibodies outside of the human body, says Meyer. So we can essentially keep up with the virus. If all goes well and the FDA gives its green light, the company intends to start testing their antibody concoctions in COVID-19 patients early next year.

Researchers at Rockefeller University are following another clue from the human bodys virus-fighting defenses. They discovered in 2017 that human cells make a protein called LY6E that can block a viruss ability to make copies of itself. Working with scientists at the University of Bern in Switzerland and the University of Texas Southwestern Medical Center, they found that mice genetically engineered to not produce the protein became sicker, and were more likely to die after infection with other coronaviruses, including SARS and MERS, compared to mice that were able to make the protein. If the mice have the protein they pretty much survive, says John Schoggins, associate professor of microbiology at the University of Texas. If they dont have it, they dont survivebecause their immune system cant control the virus. While these studies havent yet been done on SARS-CoV-2, given its similarity to the original SARS virus, theres hope a therapy based on LY6E might be useful.

Ideally, Schoggins is hoping to start testing LY6Es potential in infected human lung cells, which SARS-CoV-2 appears to target for disease. The closest mouse model for coronavirus, created to study the original SARS virus, has been retired since research on that virus dwindled after cases wanted following the 2003 outbreak. There wasnt the need to keep the mouse around, and that tells us a lot about the state of our research, says Schoggins. We dont really work on thing unless everyones hair is on fire.

Its not just immune cells that make good targets for new drugs. Other companies are looking at broader immune-system changes triggered by stressduring cancer, for example, or infection with a new virus like SARS-CoV-2that end up making it easier for a virus to infect cells. Drugs that inhibit these stress-related changes would act like molecular gates slamming shut on the cells that viruses are trying to infect.

Because SARS-CoV-2 preferentially attacks lung tissue and causes cells in the respiratory tract to launch a hyperactive immune response, researchers are exploring ways to tame that aggressive response by dousing those cells with a familiar gas: nitric oxide, often used to relax blood vessels and open up blood flow in hospital patients on ventilators who have trouble breathing. While working on a new, portable system for delivering nitric oxide developed by Bellerophon Therapeutics to treat a breathing disorder in newborns, Dr. Roger Alvarez, an assistant professor of medicine at University of Miami, got the idea that the gas might be helpful for COVID-19 patients as well. One symptom of the viral infection is low oxygen levels in the lungs, and nitric oxide is ideally designed to grab more oxygen molecules from the air with each breath and feed it to the lungs. With this system, patients dont need to be in the ICU [Intensive Care Unit] at all, he says. The patient can be in a regular hospital bed, or even at home. So you save the cost of the ICU and from a resource standpoint, you save on needing nursing care, respiratory therapists and other ICU monitoring.

In theory, if this system could be used for COVID-19 patients with moderate symptoms, it could keep those patients from needing a ventilatora huge benefit in the current context where ventilator shortages are one of the biggest threats to the U.S. health care system. So far, Alvarez has received emergency use authorization from the FDA to test a version of his system on one COVID-19 patient at the University of Miami Health System. That patient improved and is ready to go home. Its great news and gives me the information to say that this appears at least safe to study further, he says, which is what he plans to do with the first small trial of nitric oxide for COVID-19 at his hospital.

When it comes to developing a new antiviral treatment, it doesnt always pay to start from scratch. There are dozens of drugs that have become life-saving therapies for one disease after their developers accidentally discovered that the medications had other, equally useful effects. Viagra, for example, was originally explored as a heart disease drug before its unintended effect in treating erectile dysfunction was discovered, and gabapentin was developed as an epilepsy drug, but is now also prescribed to control nerve pain.

Within weeks of COVID-19 cases spiking to alarming levels in China, researchers at Gilead in Foster City, Cal., saw an opportunity. A drug the company had developed against Ebola, remdesivir, had shown glimmers of hope in controlling that virus in the laband also showed promise as a tool to treat coronaviruses like those that caused SARS and MERS. In fact, says Merdad Parsey, chief medical officer of Gilead, We knew in the test tube that remdesivir had more activity against coronaviruses like SARS and MERS than against Ebola. So it wasnt entirely surprising that when the company began testing it in people during last years Ebola outbreak in the Democratic Republic of Congo, the results were disappointing. The early studies against Ebola werent as encouraging in people as they were in animals. So we were basically on hold with the drug, waiting to see if there would be another [Ebola] outbreak to see if we could test it earlier in the infection, says Parsey.

Then COVID-19 happened. As the infection roared through Wuhan, Chinathe original epicenter of the diseaseresearchers there reached out to Gilead, knowing that the company had released data suggesting that remdeisivir had strong antiviral effects in lab studies against coronaviruses. They launched two studies of the drug in the sickest patients.

In mid-January, a man in Everett, Wash., who had recently visited Wuhan, checked into a clinic after a few days of feeling sick. He quickly went from having a fever and cough to having difficulty breathing because of pneumonia. Concerned that the man was worsening by the day, his doctor contacted the U.S. Centers for Disease Control; suspecting this might be a case of COVID-19and knowing there was no proven treatment for the infectionexperts at the agency suggested he try an experimental therapy, remdesivir.

The CDC team felt relatively confident about the drugs safety, if not its effectiveness, since Gilead had studied it extensively in animal models and, in the early trials in people, it didnt lead to any serious side effects and appeared safe. They were also aware of the companys promising data with human cells against the original SARS.

For the Washington patient, the experimental drug might be a lifesaver. A day after receiving remdesivir intravenously, his fever dropped, and he no longer needed supplemental oxygen to breathe. About two weeks after entering the hospital, he was discharged to self-isolate for several more days at home.

That set off a rush for remdesivir as cases in the U.S. went from a trickle to a flood, and doctors grasped for anything to treat quickly declining patients. Gilead initially offered the drug on a compassionate use basis, a process that allows companies, with the FDAs permission, to provide unapproved drugs currently being studied to patients who need them as a last resort. These programs are designed for one-off uses, and companies usually receive two to three requests a month from doctors . But in this case, Gilead was flooded with requests for remdesivir at the beginning of March. And because each one is evaluated on a case-by-case basis to ensure that each patient is eligible and that the potential risks of trying an untested drug dont outweigh the benefits, a backlog developed and the company couldnt respond to the requests in a timely way, says Parsey. So on March 30, Gilead announced it would no longer provide remdesivir through that program but through an expanded access program instead. Doctors can get access to the drug for their COVID-19 patients via dozens of clinical trials of remdesivir, two of which Gilead initiated. One is focused on patients with mild symptoms and one involves those with severe symptoms. The National Institutes of Health is currently heading another large study of the drug, at multiple centers around the country.

Finding a new purpose for existing drugs is ideal; they are likely already proven safe and their developers have a substantial dossier of information on how the drugs work. Thats what happened with hydroxychloroquine, a malaria drug developed after the parasite that causes the illness became resistant to the chloroquine, a drug discovered during World War II and since used widely to fight the disease. As researchers studied hydroxychloroquine in the lab in recent decades , they learned it can block viruses, including coronaviruses, from infecting cells. In lab studies, when researchers infected human cells with different viruses and then bathed them in hydroxychloroquine, those cells could generally stop viruses like influenza, SARS-CoV-2, and the original SARS virus, another type of coronavirus, from infecting the cells. The problem is that what happens in the lab often doesnt predict what happens in a patient, says Dr. Otto Yang, from the department of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at the University of California Los Angeles. In fact, in the case of influenza, the drug wasnt as successful in stopping infection in animals or in people. Similarly, when scientists brought hydroxychloroquine out of the lab and tested it in people, the drug failed to block infection with HIV and dengue as well.

Thats why doctors are approaching hydroxychloroquine with healthy skepticism when it comes to COVID-19 and are only using it on the sickest patients with no other options. Doctors at a number of hospitals, including Johns Hopkins, the University of California Los Angeles, and Brigham and Womens, for example, are starting to use hydroxychloroquine to treat patients with severe COVID-19 symptoms when they dont improve on current supportive treatments. Its not ideal, but If someone is sick in the ICU you try everything possible you can for that person, says Dr. David Boulware, a professor of medicine at the University of Minnesota, who is conducting a study of hydroxychloroquine effectiveness both in treating those with severe disease and in protecting health people from infection.

Other researchers are attempting to trace the same path with other repurposed drugs, including a flu treatment from Toyama Chemical, a pharmaceutical division of the Japanese conglomerate Fujifilm, called favipiravir, which Chinese researchers used to treat patients with COVID-19. More rigorous studies of both remdesivir and favipirivir against SARS-CoV-2 are ongoing; all researchers can say at this point is that they are worth studying further, and that they appear to be safe.

Even cancer drugs are showing promise as COVID-19 treatments, not by neutralizing the virus but by healing the damage infection does to the immune system. The Swiss pharmaceutical giant Novartis, for example, has ruxolitinib (sold under the trade name Jakavi), which was approved by the FDA in 2011 to treat a number of different cancers, and is designed to tamp down an exaggerated immune responsewhich can be caused by both tumor cells and a virus. In the case of SARS-CoV-2, a hyperactive immune response can trigger breathing problems, called a cytokine storm, that require extra oxygen therapy or mechanical ventilation. In theory, ruxolitinib could suppress this virus-caused cytokine storm. Novartis is making its drug available on an emergency use basis for doctors willing to try it on their sickest patients.

Eli Lilly is also testing one of its anti-inflammatory drugs, baricitinib, in severe COVID-19 patients. Like ruxolitinib, baricitinib interferes with the revved up signalling among immume cells that can trigger the inflammatory cytokine storm. According to president of Lilly Bio-Medicines Patrik Jonsson, there are even early hints from case studies of doctors treating COVID-19 patients that the drug may target the virus too, which could mean that it helps to lower the viral load in infected patients. The company is working with NIAID to confirm whether this is the case in a more rigorous study of severe COVID-19 patients, and expects to see results by summer.

It wasnt immediately obvious that baricitinib could potentially treat COVID-19; it took an artificial intelligence effort by UK-based BenevolentAI to scour existing medical literature and descriptions of drug structures to identify baricitinib as a possible therapy.

Such machine learning-based techniques are making the search for new therapies far more efficient than ever before. Chloroquine, hydroxychloroquines parent, came out of a massive war-time drug discovery effort in the 1940s, when governments and pharmaceutical companies combed through existing drug libraries for promising new ways to treat malaria. With computing power that is orders of magnitude greater now, its now possible to single out not just existing drugs with antiviral potential, but entirely new ones that may have gone unnoticed.

When Sumit Chanda first heard of the mysterious pneumonia-like illnesses spiking in Wuhan, China, he had an eerie feeling that the world was about to face a formidable viral foe. He had spent his entire career studying all the clever and devilish ways that bacteria, viruses and pathogens find hospitable hosts and then take up residence, oblivious to how much illness, disease and devastation they may cause. And as director of the immunity and pathogenesis program at Sanford Burnham Prebys Medical Discovery Institute in San Diego, Chanda knew that if the mystery illness striking in China was indeed caused by a new virus or bacteria, then doctors would need new ways to treat itand quickly.

So, he and his team started canvassing a 13,000 drug library, which is funded by the Bill and Melinda Gates Foundation and created by Scripps Research. Our strategy is to take existing drugs and see if they might have any efficacy as an antiviral to fight COVID-19, he says. The advantage of this approach is that you can shave years upon years off the development process and the studies on safety. We want to move things quickly into [testing] in people. In a matter of weeks, he has narrowed down the list of potential coronavirus drug candidates, and because these are already existing drugs and approved for treating other diseases, they are relatively safe, and can quickly be tested in people infected with SARS-CoV-2.

Chandas team isnt the only one taking advantage of this approach. Researchers at numerous pharmaceutical companies, biotech outfits and academic centers are screening their libraries of drugsboth approved and in developmentfor any anti-COVID-19 potential.

At Columbia University, Dr. David Ho, who pioneered ways of creating cocktails of drugs to make them more potent against HIV, is scouring a different library of virus-targeting drugs to pluck out ones that could be effective against SARS-CoV-2. Altogether, he has some 4,700 drugs (approved and in development) to look through, and he believes there is a strong chance of finding something that might be effective against not just SARS-CoV-2 but any other coronavirus that might pop up in coming years. The key, says Ho, is to be prepared for the next outbreak so the work on finding antiviral drugs doesnt have to start from scratch. We know these viruses reside in animal species, he says. We predict in the coming decade there will be more [outbreaks]. And we need to find permanent solutions. We should not repeat the mistake we made after SARS and after MERS, that once the epidemic wanes, the interest and the political will and the funding also wanes. If we had followed through with the work that had begun with SARS, we would be so much better off today.

But today, we are in the midst of a pandemic, and scientists are eager to leave no potentially promising technology untried. Banking on the growing body of science looking at how newborn babies are able to avoid life-threatening infections in their first days in the world, researchers at New Jersey-based Celularity are investigating how placental cells, rich with immune cells that protect the baby in utero, might also become a source of immune defense therapy against COVID-19. Its part of a broader strategy of cell-based treatments that scientists are beginning to explore for treating cancer as well as infectious disease.

On April 1, the company received FDA clearance for its placental cell treatment, based on a group of immune cells called natural killer cells that circulate in the placenta, and are designed to protect the developing fetus from infection. They are programmed to recognize red flags typically sent up by cells infected with viruses like SARS-CoV-2, and destroy them. After the 2002-2003 SARS epidemic, researchers in China found that people who had more severe symptoms of that disease also had deficient populations of natural killer cells.

The FDA green light means the company can launch a small human study using placental natural killer cells against COVID-19. Dr. Robert Hariri, Celularitys founder and CEO, wants to test them first in people who are infected, to see if they can stop the infection from getting worse. Our approach is to flatten the immunologic curve, he says. Our hope is to decrease the size of the viral load and keep it below the threshold of serious symptomatic disease until the patients own immune system can be revved up and respond. If those studies are encouraging, then the company will look at how natural killer cells might be used to pre-charge the immune system to prevent infection with SARS-CoV-2 in the first place.

As effective and critical as these therapies might be, they are a safety net for the best weapon against an infectious disease: a vaccine.

The main reason that a new virus like SARS-CoV-2 has such free license to infect hundreds of thousands of people around the world is because its an entirely new enemy for the human immune system making the planets population an open target for infection. But a vaccine that can prime the body to build an army of antibodies and immune cells trained to recognize and destroy the coronavirus would act as an impenetrable molecular fortress blocking invasion and preventing disease.

Unfortunately, vaccines take time to developyears, if not decades. Scientists at Johnson & Johnson are currently working on a vaccine using fragments of the SARS-CoV-2 spike protein, an easy protein target that sprinkles the surface of the virus like a crown (hence the name coronavirus, from the Latin for crown). The company loads the viral gene for the spike protein into a disabled common-cold virus vector that delivers the genetic material to human cells. The immune system then recognizes the viral fragments as foreign and deploys defensive cells to destroy it. In the process, the immune system learns to recognize the genetic material of the virus, so when the body is confronted by the actual virus, its ready to attack.

Given the manufacturing requirements to build the vaccine, and the studies in animals needed to get a hint of whether the vaccine will work, however, J&Js project is unlikely to come to fruition until mid-2021. We plan to have the first data on the vaccine before the end of the year, says Paul Stoffels, chief science officer at J&J. I would hope that in the first half of next year, we should be able to get vaccines ready for people in high risk groups like health care workers on the front lines.

That timeline is already accelerated quite a bit compared to vaccine research in non-pandemic contexts. But new technology that doesnt require a live transport system could shrink the time to human tests even further. Working with the National Institute of Allergy and Infectious Diseases, Moderna Therapeutics, a biotech based in Cambridge, Mass., developed its mRNA vaccine in a record 42 days after the genetic sequence of the new coronavirus was released in mid January. Its system turns the human body into a living lab to churn out the viral proteins that activate the immune system.

Researchers at Moderna hot wired the traditional vaccine-making process by packing their shot with mRNA, the genetic material that comes from DNA and makes proteins. The viral mRNA is encased in a lipid vessel that is injected into the body. Once inside, immune cells in the lymphatic system process the mRNA and use it like a genetic beacon to attract immune cells that can mount toxic responses against the virus. Our vaccine is like the software program for the body, says Dr. Stephen Hoge, president of Moderna. So which then goes and makes the [viral] proteins that can generate an immune response.

Because this method doesnt involve live or dead virusesall it requires is a lab that can synthesize the correct genetic viral sequencesit can be scaled up quickly since researchers dont have to wait for viruses to grow. Almost exactly two months after the genetic sequence of SARS-CoV-2 was first published by Chinese researchers, the first volunteer received an injection of the Moderna vaccine. The companys first study of the vaccine, which will include 45 healthy participants, will monitor its safety. Hoge is already gearing up to produce hundreds and thousands of more doses to prepare for the next stage of testing, which will enroll hundreds of people, most likely those at high risk of getting infected, like health care workers.

If those results arent as promising as health experts hope, there are other innovative options in the works. At the University of Pittsburgh, scientists who had been developing a vaccine against the original SARS virus have switched to making a shot against the new one. Their technology involves hundreds of microneedles in a band-aid like patch that deliver parts of the coronavirus protein directly into the skin. From there, the foreign viral proteins are swept into the blood and into the lymph system, where immune cells recognize them as invaders and develop antibodies against them. After seeing animals inoculated with their vaccine develop strong antibodies against SARS-CoV-2, the team is ready to submit an application to the FDA to begin testing in people.

Whats different about these new coronavirus efforts is the fact that they arent all designed to control SARS-CoV-2 alone. Recognizing that this coronavirus is the third in recent decades to cause pandemic disease, scientists are focusing on building therapies, including vaccines, that can quickly be adapted to target different coronaviruses that might emerge in coming years. We hope these new technologies become the kinds of things we build in our tool kits that as humans will allow us to respond in a much more accelerated way to the next pandemic, says Modernas Hoge. Because we expect continuing threats from viruses in the future.

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Vaccines, Antibodies and Drug Libraries. The Possible COVID-19 Treatments Researchers Are Excited About - TIME

Researchers discover a novel role for dopamine that impacts gene expression related to cocaine abuse. – Brinkwire

Scientists at the Icahn School of Medicine at Mount Sinai have discovered a new role for the brain chemical dopamine that is independent of classic neurotransmission. The new role appears to be critical to changes in gene expression related to chronic exposure to, or abuse of, cocaine, according to a study published Friday, April 10, in the journal Science.

Our study provides the first evidence of how dopamine can directly impact drug-induced gene expression abnormalities and subsequent relapse behavior, says Ian Maze, Ph.D., Associate Professor of Neuroscience, and Pharmacological Sciences, at the Icahn School of Medicine at Mount Sinai, and lead author of the study. Beyond transmission of signals between neurons in the brain, we have found that dopamine can be chemically attached to histone proteins, which causes cells to switch different genes on and off, affecting regions of the brain that are involved in motivation and reward behavior. This biochemical process significantly affects cocaine vulnerability and relapse when perturbed by drugs of abuse.

The study revolves around DNA and how it works to form each persons individual biological map. Each cell in the body contains two meters of DNA, the blueprint for all functions of all cells in the body. This DNA is wound around spools of histone proteins (proteins that package DNA in the nucleus of cells, and are heavily prone to chemical modifications that aid in the regulation of gene expression) into structures referred to as nucleosomes. When DNA encoding a specific gene is wound tightly within the spool, that gene is less likely to be expressed. When the gene is not wound as tightly, it is more likely to be expressed. This can affect many functions of a given cell.

Dopamine, known as the feel-good neurotransmitter, is a chemical that ferries information between neurons. The brain releases it when we eat food that we crave or while we have sex, contributing to feelings of pleasure and satisfaction as part of the natural reward system. This important neurochemical boosts mood, motivation, and attention, and helps regulate movement, learning, and emotional responses. Dopamine also enables us not only to see rewards but to take action to move toward them.

Vulnerability to relapse during periods of cocaine withdrawal is believed to result from functional rewiring of the brains reward circuitry, particularly within mid-brain regions, such as the ventral tegmental area (VTA). The research team discovered that a protein called transglutaminase 2 can directly attach dopamine molecules to histone proteins (a process called histone dopaminylation or H3Q5dop) which, in turn, affects the histone-DNA spool to enable environmentally regulated alterations in gene expression. They found that histone dopaminylation plays a critical role in fueling heightened vulnerability to relapse over a prolonged period of time. Specifically, accumulation of H3Q5dop in the VTA can, in effect, hijack the reward circuitry, making it difficult to distinguish between good and maladaptive behavior. The study found, however, that reducing H3Q5dop in rats programmed to undergo withdrawal from cocaine significantly reversed cocaine-mediated gene expression changes and reduced cocaine-seeking behavior.

The question that has always challenged neuroscientists is, what are the underlying molecular phenomena that drive increased vulnerability to drug relapse in people, says Ashley Lepack, Ph.D., a researcher in the Department of Neuroscience, The Friedman Brain Institute, in Dr. Mazes lab at Mount Sinai, and first author of the study. Our research is shedding valuable light on this area by identifying histone dopaminylation as a new, neurotransmission-independent role for dopamine that hasnt been implicated before in brain pathology.

We believe these findings represent a paradigm shift in how we think of dopamine, not just in the context of drug abuse, but also potentially in other reward-related behaviors and disorders, as well as in neurodegenerative diseases like Parkinsons, where dopamine neurons are dying, says Dr. Maze. In this case, the question becomes, could this neuronal death be due, in part, to aberrant dopaminylation of histone proteins?

In a study published last year, Dr. Maze and his team found that another neurotransmitter, serotonin, a chemical involved in the regulation of mood, acts in a similar way as dopamine on gene expression inside brain cells.

When we observed this unique signaling mechanism with serotonin, we decided to look at other neurotransmitters, particularly dopamine, and found that it could also undergo this type of chemical modification on the same histone protein, explains Dr. Maze.

Early-stage work with human post-mortem tissues has demonstrated to Dr. Maze that strong parallels may well exist, but that basic questions around biochemical function still remain before human trials can begin. From a therapeutic standpoint, weve started to identify from rodent models the mechanisms that can actually reverse aberrant and addictive behaviors, says Dr. Maze, and that knowledge could be vital to moving this novel research into the clinic.

Provided byThe Mount Sinai Hospital

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Researchers discover a novel role for dopamine that impacts gene expression related to cocaine abuse. - Brinkwire

A letter to the editor genetic data and law enforcement bias – The Ticker

This letter to the editor was submitted by Max Blankfeld, the chief operating officer of Gene By Gene/FamilyTree DNA, regarding an article published by The Ticker's science section about the company sharing genetic data to law enforcement.

FamilyTreeDNA does not share genetic data with law enforcement. It is also true that FamilyTreeDNA does allow law enforcement to submit crime-scene DNA to its matching database.

The fact that both statements are true has confounded the media, resulting in incorrect and misleading reporting, as was the case with The Ticker Science article titled, "Is Testing Your Ancestry Safe?" FamilyTreeDNA matching database does not share genetic data with any third party, including law enforcement.

The DNA matching process is completely automated and the only information shared between DNA matches for customers who consent to participate in the matching process is a public profile information controlled by the customer and the estimated relationship between matches based on the number of shared centimorgans.

FamilyTreeDNA does not share, sell or barter the genetic data of its customers with any third party.

In the year 2000, FamilyTreeDNA, the pioneer of the Direct-to-Consumer genetic testing, started offering a service that allows people to find relatives and ancestral origins.

This was geared towards genealogists, who after encountering a roadblock with their traditional genealogical tools, resorted to the matching tool that we developed, which allows two individuals to see if they have enough DNA in common to claim a close relationship.

The success of this initiative not only led other companies to follow suit, but other groups of people started using it: adoptees who wanted to find biological relatives and ancestral origins, sperm- donor children who wanted to find half-siblings and more recently, law enforcement, who wanted to see if, through genetic matches to crime scene DNA, they could get hints that would lead them to the potential criminal or to identifying a victim.

In the cases of murder or sexual assault, DNA matches provide an investigative lead for law enforcement to follow, enabling the identification of suspected perpetrators faster than ever before.

In none of the above cases is the FamilyTreeDNA database searched or searchable.

Each individual that tests with us has a password-protected page where they can only see those whose DNA has a minimum level of matching. When we realized that law enforcement was using this tool, FamilyTreeDNA could have simply turned a blind eye or been subject to subpoenas.

Instead, we created a process for oversight through formal registration and submission of crime-scene samples. In conjunction with law enforcement and with the supervision of a Citizens Panel composed of representatives of our customers and a professor of bioethics at the Baylor College of Medicine, we developed the Law Enforcement Guide, which is publicly available at https://www.familytreedna.com/legal/law- enforcement-guide.

In the past week, law enforcements use of FamilyTreeDNAs matching database has led to a serial murder confession in Clearfield, Utah and the release of a man who spent the last twenty years in a California jail for a crime he did not commit.

In the 20 years since the inception of FamilyTreeDNA, we are proud to have helped thousands of customers find long lost relatives.

Now, we are proud of fulfilling a public safety role in helping identify perpetrators of heinous crimes like rape and murder, identification of their victims and the exoneration of the falsely accused and imprisoned.

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A letter to the editor genetic data and law enforcement bias - The Ticker

IQVIA Report: Spending on Drugs Globally to Exceed $1.1 Trillion by 2024 – BioSpace

The IQVIA Institute for Human Data Science just released their latest report, Global Medicine Spending and Usage Trends: Outlook to 2024. Among many of the insights provided include that global medicine spending is projected to increase from 2 to 5% annually through 2024 on a net basis, compared to 4.2% in the past five years. Global medicine spending is expected to exceed $1.1 trillion by 2024.

Murray Aitken, IQVIA senior vice president and executive director of the IQVIA Institute for Human Data Science, took time to speak with BioSpace about the report ahead of publication.

The report draws upon IQVIA proprietary data sets. Those data sets are based on a number of different sources of information, including pharmaceutical wholesalers who handle the physical distribution of medicines," Aitken said. "We work with those wholesalers around the world in over 100 countries to gather information about their shipments of pharmaceuticals to retail pharmacies and hospitals, for example. Thats the foundation for the data we use.

In addition, Aitken emphasized, wanting to make sure readers of the report understand, that they are utilizing slightly different metrics for this report. One, he said, is we have reported the size of the market on a net price basis, which is different than weve done before, where we havent been able to fully estimate the impact of rebates and discounts. In 2019, we estimate those were $255 billion. In 2024 we estimate they are up to $400 billion and we have taken those off the market size to arrive at a net market size.

Another is the use of defined daily dose (DDD), which is a measurement that converts every type of drug and how its delivered, whether thats via pills, vials, patches, creams, etc., into a clearly defined daily dose. This allows readers and various stakeholders to more accurately assess the use and cost comparisons for drugs if dosing lasts various amounts of time, whether a year, a month or an hour.

One important finding from the report is that although spending on medicines continues to rise from its current level of $935 billion in 2019 to $1.1 trillion in 2024 (on a net price basis), thats actually a slower rate of growth than has been seen over the past five years.

Aitken believes there are two main factors for the slowing.

First is that we are seeing payers attempt to constrain growth in their budgets, Aitken said.

As a result, they are decreasing their budgets and doing so with aggressive negotiations with drug manufacturers. They may also restrict access or limit access to certain drugs for only certain patients. This is not a new trend, Aitken noted, but we see it becoming more intense each year.

As such, they expect to see new prices for branded drugs either fall by 1% or increase by 2%, somewhere in that range. Thats down from the levels weve seen historically, Aitken said.

And in other developed countries, the report projects pricing to decline by between 2 and 5%.

The second factor is that many drugs are expected to lose patent protection or some other form of exclusivity over the next five years. Aitken said, The impact there will be to reduce the market for those branded drugs by about $139 billion over the next five years, compared to $107 billion reduction that we saw in the past five years. Weve got more impact bringing down growth from the effects of drugs losing exclusivity and having generics or biosimilars entering the market.

On the other hand, the report notes a very healthy research-and-development pipeline thats producing new drugs. Its not expanding the market faster than the impacts of the price reductions and patent expirations.

Another significant trend is adoption of specialty medicines, which is driving increased spending. Currently specialty medicines make up about 36% of global spending on medicines and are projected to make up 40% by 2024.

The IQVIA report defines specialty medicines as those that treat chronic, complex or rare diseases and have a minimum of four out of seven of the following additional characteristics: cost more than $6,000 annually, are initiated or subscribed by a specialist physician, are not self-administered, require special handling in the supply chain, require patient payment assistance, are distributed through non-traditional channels, such as specialty pharmacies, and the therapies have significant side effects that require additional counseling or monitoring.

Aitken said, Its broader than gene therapies, and includes most biologics, and gene and cell therapies, but also some small molecule drugs, such as targeted therapeutics for cancer.

He added, When we look at the pipeline, we see a growing concentration on specialty drugs, including biologics, including what we call next-generation biotherapeutics, which is where cell and gene therapies fall. We also see a lot more focus for drugs treating rare diseases or drugs for disease areas where there are no effective treatments today.

This is a long-term trend that has been playing out for at least the last decade, reflected both in drugs coming into the market over the past few years as well as the pipeline compounds currently working their way through clinical development that will be launched in the next three to five years.

I think the payers, Aitken said, are under pressure because weve got more therapies becoming available that can help extend life, improve the quality of life, reduce the need for social services or other types of medical care, but they put pressure on the drug budgets.

Patients will often benefit, because globally they will likely have greater access to new medicines, although they may come at a higher cost. For healthcare providers, they will have expanded treatment options and new technologies, but they will have higher price tags that target patients with critical unmet need, which will likely bring additional administrative burdens to handle new innovative payment strategies.

And for drug manufacturers, they can expect to see continuing pricing and market access controls that will affect uptake of novel drugs at launch and require evolving investments and efforts to optimize the medicines adoption.

The future is bright but will come with challenges. Aitken noted, The number of daily doses of drugs that are consumed globally is currently at about 1.8 trillion doses, up from 1.6 trillion five years ago. The volume is rising fastest in those drugs used to treat noncommunicable diseases, which includes cardiovascular disease, diabetes, respiratory disorders, and cancer.

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IQVIA Report: Spending on Drugs Globally to Exceed $1.1 Trillion by 2024 - BioSpace

New sickle cell disease treatments are helping people live longer and giving them a higher quality of life – PhillyVoice.com

Treatment for sickle cell disease has come a long way since the 1970s when the life expectancy of people living with it was less than 20 years.

People with sickle cell disease are not only living longer life expectancy is now 42 to 47 years of age but are enjoying a better quality of life, too.

"In the Philadelphia area, there has been great pediatric care for sickle cells disease and because of that people who have it are living very well," said Dr. Farzana Sayani, a hematologist at Penn Medicine.

Sayani is the director of a comprehensive sickle cell program focusing on adults living with the disease. Penn also has an active transition program for youth transitioning from a pediatric institution to adult care.

Sickle cell disease is an inherited red blood cell disorder that affects about 100,000 Americans.It is most often found in people of African or Hispanic descent.About 1 in 365 African-American babies are born with sickle cell disease, according to Sayani.

People who have the disease inherit an abnormal type of hemoglobin in their red blood cells, called Hemoglobin S, from both their mother and father.When only one parent has the hemoglobin S gene, a child will have the sickle cell trait, but usually does not develop the disease. But they may pass it on to their children.

Hemoglobin is the protein in the blood responsible for carrying oxygen to the rest of the body. Hemoglobin S causes red blood cells to become stiff and sickle-shaped. Instead of being round in shape, they look like crescent moons.

Sickle cells are sticky and can bind together, blocking the flow of blood and preventing oxygen from getting where it needs to go in the body. This causes sudden attacks of pain referred to as a pain crisis.

There are severaldifferent types of sickle cell disease.Hemoglobin SS, also known as sickle cell anemia, is the most common and most severe type of sickle cell disease.

Anemia occurs when red blood cells die at a rate faster than the body can replace them. Normal red blood cells generally live for 90 to 120 days. Sickled cells only live for 10 to 20 days. This shorter life-to-death cycle is harder for the body to sustain.

Another form,Hemoglobin SC, is not as severe as sickle cell anemia, but it can still cause significant complications, Sayani said.Other forms include Hemoglobin S0 thalassemia, Hemoglobin S+ thalassemia, Hemoglobin SD and Hemoglobin SE.

Sickle cell disease screening is a mandatory part of newborn screenings in Pennsylvania.

If the screening is positive, the family is informed and plugged into the health care system in order to receive the proper care.

If the disease is not diagnosed at birth, a blood test can confirm it at any age in which symptoms start to surface.

The severity of sickle cell disease can vary.

Each individual is affected differently, making it difficult to predict who will get what complications, Sayani said. That is why a comprehensive sickle cell program is so important.

Early signs include a yellowish tint to the skin or jaundice, fatigue and a painful swelling of the hands and feet.

"Young children with sickle cell disease may be tired, not eat very well and have delayed growth," Sayani said. "They may also develop anemia, be at greater risk of infection and start to experience pain crises."

Acute pain crises, also known as vaso-occlusive crises, can lead to long stays in the hospital to manage the crippling pain. Children with sickle cell disease also tend to experience delayed growth and puberty.

As a person with sickle cell disease grows older, the sickled red blood cells start to affect various organs, bones and joints.

This can lead to acute chest syndrome, which occurs when damaged lung tissues makes it difficult to breathe. Brain complications, including stroke, are possible.People with sickle cell disease are also prone to heart damage, eye problems, and infections like chlamydia, salmonella and staphylococcus. Chronic and acute pain is common.

There are different types of medicine that can help manage sickle cell disease.

Last year, an oral medicine was approved that makes sickle cells less likely to sickle. So was an intravenous medicine that has been shown to reduce pain crises and hospitalizations by 50%. Some people living with sickle cell disease also may need regular blood transfusions.

Hydroxyurea has also been used successfully for many years to reduce pain crises and the need for blood transfusions and hospitalizations.

Currently, blood and bone marrow transplant is the only way to cure the disease. But it is not an option for everyone because of the difficulty of finding a well-matched stem cell donor.

A related donor is best but only about a third of sickle cell patients have a donor that is related and fully-matched, Sayani said.

While these transplants have a 85% or more success rate, they also are associated with significant risks, including organ dysfunction, infection and graft vs. host disease which can be quite debilitating.

Transplants completed in children have the best results, Sayani said. But because of the risks involved, doctors only suggest it for patients with severe forms of the disease.

Early clinical trials with gene therapy are also showing promise, she added.

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New sickle cell disease treatments are helping people live longer and giving them a higher quality of life - PhillyVoice.com

With the help of Chan Zuckerberg Initiative, U of T researchers develop data tools to accelerate science – News@UofT

Which genetic changes predispose to disease? How do characters in a novel relate to each other? Which wine and cheese go well together?

Turns out, theres an app for that and its about to become far more versatile as University of Toronto researchers work to release it to a wider community with the support of the Chan Zuckerberg Initiative.

CalledCytoscape, the software in question is already an essential tool for viewing networks in biology, including gene networks that hold clues about how different genes co-operate to sustain health and how these networks change in disease. But like most research software, its currently a desktop application that has to be installed and updated, and doesnt work on phones or tablets.

Today, the Chan Zuckerberg Initiative announced it is providingU of TsGary BaderandHannesRst, both researchers at the Donnelly Centre for Cellular and Biomolecular Research, with US$150,000 each to create a cloud-based Cytoscape and Open MS.Co-founded by Facebook chief executive Mark Zuckerberg and his spouse, Priscilla Chan, the initiative seeks to harness technology to accelerate progress in science.

The future of data analytics should be that it is easier to do, easier to share information and it should be easier for people to collaborate, says Bader, a professor of computational biology who is cross-appointed to the department of molecular genetics in the Faculty of Medicine and the department of computer science in the Faculty of Arts & Science, andholds the Ontario Research Chair in Biomarkers of Disease.

Just as web-based cloud computing has transformed how we listen to music and store data, Bader, whose team is developing the web-based Cytoscape Explorer, says that freedom fromhaving to keep track of files and e-mail them back and forth will boost creativity and speed up science.

Because your document lives on the cloud, the latest version is already there, and you can access it anytime, anywhere. It makes it easier to see what everyone else is doing and youre exposed to more ideas that changes the way you do things in a positive way.

Initially designed for genomics researchers, Cytoscape incorporates the basic principles of network theory and can be easily adapted for other applications. Besides biology, it has been used in business, social studies and marketing, as well as mapping how characters in an epic science fiction novel relate to each other.

We are building the foundation for other people to do research,saysHannesRst,an assistant professor of computational biology at the Donnelly Centre(photo by Jovana Drinjakovic)

Bader even adapted the softwareto find optimal wine and cheese combinations for a dinner party.

Research analytics have been slow to move to the cloud because it is difficult to obtain funding purely for software development unless it promises to reveal new insights. Yet cloud analytics are desperately needed to support increasingly collaborative research often involving teams scattered around the world.

We are building the foundation for other people to do research, says Rst, an assistant professor of computational biology who is also cross-appointed to the departments of molecular genetics and computerscience, and whose team is developingOpenMS, a free tool for biomarker analysis.

With more than one million downloads since launching in 2001, Cytoscapes popularity is only likely to grow with the move to the cloud.

We really think that making this available on the web will allow users who never previously discovered the software, and never used it on the desktop, to easily access it, says Bader, who joined the Cytoscape team in the early 2000s and is leading the newly funded project with Dexter Pratt, a software engineer in the group of Trey Ideker, a professor at the University of California, San Diego, and a co-founder of Cytoscape.

If scientists knew what healthy looked like at the molecular level, they might be able to spot disease as it begins to develop and potentially halt it.

Molecular profiling of human tissue blood, for example produces vast amounts of complex data calling for sophisticated analysis tools such as OpenMS, a leading free software for the analysis of data produced by mass spectrometry, which identifies and counts molecules based on their unique mass-to-charge ratio.

Composed of a set of algorithms that can be rearranged into different workflows, Open MS can be tailored to individual user data. Butin its current form, it requires a certain level of coding knowledge, discouraging uptake among users without programming experience.

The cloud version will have no such obstacles.

We want to make OpenMS user-friendly, using a graphic user interface where users can click on buttons to start their analysis instead of typing commands on the command line, says Rst, who holds the Canada Research Chair in Mass Spectrometry-based Personalized Medicine.

Programming-savvy users will be able to inspect and modify the source code to their needs.

To set up OpenMS on the cloud, Rst will take advantage of so-called Docker containers, which are sets of code that enable standardized software packaging so that it runs the same way on any platform.

The software will be hosted on Niagara, a supercomputer cluster at U of T and part of ComputeCanada, the high-performance computing infrastructure established by the federal government.

The overarching goal of Rsts research is to identify early biomarkers of diabetes and cancer.

We want to take peoplesbody fluids and generate a metabolic profile that we can track over time how people change, he says.

His team recently acquired a state-of-the-art mass spectrometry instrument worth $1 million, with support from the Canada Foundation for Innovation and U of Ts Faculty of Medicine. The instrument, referred to among lab members as the space ship for its futuristic look, can detect trace amounts of biomolecules for more accurate profiling.

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With the help of Chan Zuckerberg Initiative, U of T researchers develop data tools to accelerate science - News@UofT

A man from Wales is having his genes altered to fight his blood cancer – Wales Online

A pensioner has become the first patient in Wales to undergo a ground-breaking gene treatment for blood cancer.

CAR-T (chimeric antigen receptor T-cell)therapy, carried out at the University Hospital of Wales (UHW) in Cardiff, involves changing cells in the immune system to recognise and destroy cancer cells.

The success of the therapy has been described as a "significant day for precision medicine in Wales".

John Davies, 71, from Blackwood , was diagnosed with lymphoma five years ago following a routine check-up and was chosen as the first patient to have the treatment.

The retired civil servant, who has had other previous unsuccessful treatment for his lymphoma, underwent a series of stringent tests to ensure his suitability for this treatment.

Blood samples were collected from Mr Davies for six hours. His healthy T-cells were then separated and transported in a special cooling box to Amsterdam where his they will be stored and transported to California for modification.

The engineered cells will then be transported back to Amsterdam and then to UHW to be administered to the patient in a months time.

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Mr Davies said: "After previously failed treatments, I feel lucky to have been offered this opportunity. I feel like a pioneer and if sharing my story can help other people, then I am happy to do it."

CAR-T therapy is described as a "complex yet personalised" immunotherapy based on the individual patient.

The process involves taking healthy T-cells from the patient and engineering them to recognise cancer cells.

They are then reintroduced intravenously into the patient to fight off cancer and restore the normal function of their own immune system.

Our immune system works to protect the body against infection, illness and disease. It can also protect us from the development of cancer.

The immune system includes the lymph glands, spleen and white blood cells. Normally, it can spot and destroy faulty cells in the body, stopping cancer developing.

But a cancer might develop when:

Immunotherapy uses our immune system to fight cancer. Itworks by helping the immune system recognise and attack cancer cells.

Some types of immunotherapy are also called targeted treatments or biological therapies. You might have immunotherapy on its own or with other cancer treatments.

Dr Keith Wilson, lead clinician and consultant haematologist at UHW said: "This is a significant day for precision medicine in Wales. It has taken 18 months of hard work from an incredible team of researchers, clinicians, support staff and partners to make today even possible.

"About 50% of patients will respond positively to CAR-T treatment so the next stage after the engineered cells are reintroduced into the patient will be to monitor their progress closely.

"With each treatment created specifically for the individual patient, its truly a ground-breaking treatment at the forefront of personalised medicine. This is precision medicine at its best."

The treatment was made possible thanks to funding from WHSCC (Welsh Health Specialised Services Committee) through the New Treatment Fund set up by the Welsh Government in 2017.

The aim of the fund is to deliver advanced treatments, such as cell and gene therapies, for patients with chronic and terminal conditions that are resistant to current treatment and medications.

Staff at Velindre University NHS Trust, the Welsh Blood Service, WHSCC and Cardiff and Vale University Health Board's haematology team were all involved in the development.

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A man from Wales is having his genes altered to fight his blood cancer - Wales Online