Category Archives: Gene Medicine

PARIS & LEIDEN, Netherlands--(BUSINESS WIRE)--HORAMA SA, a French biotechnology company focusing on gene therapy for the treatment of rare genetic diseases in ophthalmology, announced today an exclusive licensing agreement with the Leiden University Medical Center (LUMC) for global rights to a gene therapy program to treat the Inherited Retinal Dystrophy associated with pathogenic CRB1 gene mutations, a rare but devastating ophthalmic condition leading to blindness

"We are excited to enter into this agreement with the LUMC, a leading academic institution with highly recognised scientific leaders in the field of gene therapy such as Jan Wijnholds, to expand our leadership in gene therapy. This collaboration enables us to expand our pipeline of gene therapy treatments for ophthalmic conditions for which there is a high unmet medical need, commented Christine Placet, CEO of HORAMA.

Our studies in the last 20 years resulted in the development of a platform for candidate gene therapy medicines for children with pathogenic CRB1 mutations. The main obstacle to test our novel innovative medicine gene therapy products in clinical studies was the high costs of the clinical development phase. We are, therefore, excited about this research agreement with HORAMA team, which is a global expert in this field, commented Jan Wijnholds, LUMC.

Under the agreement, HORAMA will receive an exclusive worldwide license to certain patent rights and know-how for the drug candidate (referenced as HORA-001). In return for these rights, LUMC will receive an undisclosed upfront payment, milestone payments and royalties on net sales of products. HORAMA shall be responsible to bring the gene therapy to market with completion of the non-clinical and clinical studies. Based on current timelines, and subject to regulatory review, HORAMA expects initiating a Phase I/II clinical study with HORA-001 in 2023.

Per the agreement, the parties have entered into a non-clinical development agreement with Leiden University Medical Center (LUMC), led by Dr. Jan Wijnholds, Team Leader and permanent staff member at the LUMC Department of Ophthalmology.

About HORAMA

At HORAMA, we believe in gene therapy to treat a broad range of inherited disorders.

Our focus is on Inherited Retinal Dystrophies with our lead clinical program targeting patients with PDE6B gene mutations, a condition which leads to progressive vision loss in children and adults ultimately leading to legal blindness.

Our team is pushing the boundaries of gene therapy by advancing next generation delivery platforms that will improve effectiveness and coverage of gene transfer to address multiple diseases. For more information, please go to: http://www.horama.fr.

Gene therapy market (source: FiorMarkets and Grand View Research, Inc)

Gene therapy is being developed with an aim to treat rare conditions with limited or no treatment options.

Genetic disorders occur due to gene mutations, which can result in incorrect protein synthesis. Gene therapy is used to introduce a healthy gene into cells to allow the synthesis of a functional protein. Growing awareness and acceptance of gene therapy for various disease treatments are favouring market growth.

The global gene therapy market is estimated to reach $5.5 billion by 2026, while the global ophthalmology market is projected to grow to $43 billion by 2026 (April 2019 report issued by Grand View Research, Inc.).

Inherited Retinal Dystrophies

Inherited Retinal Dystrophies (IRD) represent a diverse group of progressive visually debilitating diseases that can lead to blindness. In patients with an IRD, mutations in genes, which are critical to retinal function, lead to progressive, direct or indirect photoreceptor cell death and associated visual function losses.

IRDs are a genetically heterogeneous group of diseases, with over 260 genes identified to date, IRDs associated with pathogenic CRB1 gene mutations are among this heterogeneous group, similar to the autosomal recessive IRD associated with pathogenic PDE6B gene mutations.

About CRB1

CRB1 gene mutations are a major cause of early onset and delayed onset IRD. Proteins such as CRB1 and CRB2 are essential in the retina to maintain adhesion between photoreceptors and Mller glial cells. Loss of CRB function results in loss of photoreceptors and causes blindness.

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HORAMA Signs Exclusive License Agreement with Leiden University Medical Center Targeting CRB1 Gene Mutations to Treat Inherited Retinal Dystrophies -...

Jane Pei-Chen Chang,1,* Kuo-Hao Huang,1,* Chieh-Hsin Lin,2,3 Hsien-Yuan Lane1,3,4

1Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan; 2Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; 4Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan

*These authors contributed equally to this work

Correspondence: Chieh-Hsin LinDepartment of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Road, Niaosong District, Kaohsiung 833, TaiwanTel +886-7-7317123 ext. 8753Fax +886-7-7326817Email cyndi36@gmail.com

Hsien-Yuan LaneDepartment of Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 404, TaiwanTel +886-4-22062121 ext. 1074Fax +886-4-2236-1230Email hylane@gmail.com

Background: Visual learning plays an important role in general populations and patients with schizophrenia. Genetic influences on visual learning remain unknown. Two functional single nucleotide polymorphisms (SNPs), Ser704Cys of the DISC1 gene and M24 (rs1421292) of the G72 gene, are strongly associated with pathogenesis and pathophysiology of schizophrenia. This study examined these two SNPs effects on visual learning in schizophrenia patients.Methods: Two hundred seventy-one patients (mean age, 37.0 years [SD = 9.3]; 159 men) with chronic schizophrenia were genotyped for the DISC1 Ser704Cys and G72 M24 SNPs and assessed for visual learning with Visual Reproduction II (delayed reproduction) of Wechsler Memory Scale III (WMS-III). For comparison, verbal learning (using Wordlist II of WMS-III) and attention (by Continuous Performance Test) were also measured.Results: The DISC1 Ser carriers excelled DISC1 Cys/Cys homozygotes in visual learning (p=0.004, effect size: 0.43), but not in other cognitive functions. G72 M24 A-allele carriers and G72 M24 T/T homozygotes performed similarly (effect size: 0.07). In SNP-SNP interaction analysis, the patients with Ser carrier_T/T had better visual learning than those with Cys/Cys_T/T (p=0.004, effect size: 0.70) and those with Cys/Cys_A-allele carrier (p=0.003, effect size: 0.65). Education had a positive effect (p=0.007), while negative symptoms had a negative effect (p< 0.001) on visual learning.Conclusion: The findings suggest that genetic variations in DISC1 Ser704Cys and G72 M24 affect visual learning in schizophrenia patients. The effect sizes of SNP-SNP interaction surpassed the sum (0.50) of effect sizes from two individual genes, suggesting synergistic DISC1-G72 interaction.

Keywords: attention, DISC1, G72, visual and verbal learning, schizophrenia

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Genetic Effects of DISC1 and G72 (DAOA) on Visual Learning of Patients | NDT - Dove Medical Press

Yousuf Khan is PhD student in molecular and cellular physiology at Stanford School of Medicine. He is the first author on a recent article published in BMC Genetics which outlines the discovery of a novel overlapping coding sequence in the gene POLG. His work, combined with other research in the field, may suggest that there is an abundance of overlapping open reading frames.Technology Networks recently spoke with Khan to learn more about the research study, how genetics can be likened to cooking up a recipe, and an accidental discovery that could lead to an exciting collaboration in this field.

Molly Campbell (MC): For our readers that may be unfamiliar with genomics, open reading frames and bioinformatics, can you tell us about the background of your research?Yousuf Khan (YK): Lets compare the expression of a genetic sequence with cooking a meal. TheDNAis our motherscookbook, it contains every single possible recipe that we would ever need. But when we want to prepare a meal, we dont want to get our precious cookbook dirty. So instead, we store the cookbook in a different location (genomic DNA in eukaryotes is inside the nucleus). When we want to make something, we make aphotocopyof a page in the cookbook (the cell creates amessenger RNA, a temporary copy, of a portion of DNA).

This process of copying a portion of theDNAintomRNAis called transcription. We then take oursingle sheet of our photocopied recipe(ourmRNA) and take it back into the kitchen (thecytoplasmof the cell).

In thekitchen(cytoplasm), we read thephotocopied recipeone step at a time. By reading thephotocopied recipefrom thefirst step to the last step(the open reading frame), we convert the instructions into our finished,delicious meal. In a similar manner,mRNAis read and translated into aproteinby a machine called a ribosome.In the traditional way we understand biology, cells that want to create different proteinsjust alternatively splice differentmRNAsto be translated. This would be the equivalent of photocopyingrecipesfor scrambled eggs, pancakes, and bacon on Monday morning and then photocopying a different set ofrecipes(e.g. mashed potatoes, steak, and salad) for dinner.

MC: Can you expand on your recently published study? Have you essentially discovery a "gene within a gene"? If so, does this point towards a potentially "hidden" genome?YK: In our article, we found that the gene POLG creates an mRNA that contains a very long overlapping open reading frame. Imagine youre following the instructions of a recipe to make lasagna; you start with step one and you complete every step until you reach the last step. But if you started at step two and then completed steps three, four, five, and six, you would create a hamburger instead. So encoded within a single photocopied recipe, there are multiple meals that can be made.

This study and others that have been published previously may suggest that there are an abundance of these overlapping open reading frames. The real effort is finding them and characterizing them!

MC: What were the key challenges you encountered in this research?YK: The real challenge is finding these overlapping sequences. Theyre tricky to detect and it would not have been possible to do this work without the support of the amazing researchers at Ensembl.

MC: What are your next steps in this space?YK: I think there are more of these "hidden genes" to be found. The two important questions are i) where exactly are they? and ii) how are they read?

MC: On Twitter, you said "This finding was also made by another group at the exact same time, whose manuscript will be up shortly as well" Will your research group be looking to collaborate?YK: This is actually a funny story. I was at a conference in Germany last September and I was sitting in the audience listening to a talk. As my focus began to wane, I started leafing through the abstract book seeing what other research was going to be presented at the conference. Right in front of me on a completely random page I turned to was almost exactly my research. The only difference was that it was done by a completely different group. I panicked. However, after an email of advice from adviser, I decided to approach the group and we ended up agreeing on trying to coordinate our submissions. My work was accepted to a journal faster and hence they uploaded their manuscript to a preprint server after I told them my paper was up. The link for their work is here.

Yousuf Khan, PhD researcher at Stanford School of Medicine, was speaking to Molly Campbell, Science Writer, Technology Networks.

Reference: Khan et al. (2020). Evidence for a novel overlapping coding sequence in POLG initiated at a CUG start codon. BMC Genetics. DOI: https://doi.org/10.1186/s12863-020-0828-7.

The rest is here:
Novel Discovery of "Hidden" Gene Within a Gene in Mammals - Technology Networks

Majority of potential study participants have been pre-screened

EB-101 successfully manufactured at Abeona and transplanted at Stanford University Medical Center

NEW YORK and CLEVELAND, March 17, 2020 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (ABEO), a fully-integrated leader in gene and cell therapy, today announced that investigators at Stanford University Medical Center have treated the first patient in the pivotal phase III VIITAL study evaluating EB-101, the Companys gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa (RDEB).

Treating the first patient in our pivotal Phase III VIITAL study is an important achievement for the EB-101 program, now the most advanced gene therapy program in RDEB, said Joo Siffert, M.D., Chief Executive Officer. This achievement confirms that Abeona can deliver EB-101 in a study setting that closely parallels its potential real-world application. We remain confident that VIITALTM will replicate results from the Phase I/II trial demonstrating that EB-101 treatment resulted in sustained and durable wound healing with a favorable safety profile.

The VIITALPhase III study is a multi-center, randomized clinical trial assessing EB-101 in up to 15 RDEB patients, with approximately 30 large, chronic wound sites treated in total. The primary outcome measure is wound healing, comparing treated with untreated wound sites on the same patient.Secondary endpoints include the assessments of pain, as well as other patient reported outcomes. Investigators at Stanford University Medical Center are currently enrolling eligible patients into the VIITALTM study and preparations for an additional clinical site initiation are ongoing. Additional information about the trial is available at abeonatherapeutics.com/clinical-trials/rdeb.

Abeona is producing EB-101 for the VIITALTM study at the Elisa Linton Center for Rare Disease Therapies, its fully-functional gene and cell therapy manufacturing facility centrally-located in Cleveland, OH. The 26,000 ft2 center is housing large-scale cGMP capacity for AAV gene therapy and EB-101 cell therapy manufacturing, and state-of-the-art laboratories to support CMC development for process and analytics, all of which is validated and governed by comprehensive quality systems and overseen by experienced staff.

About EB-101EB-101 is an autologous, gene-corrected cell therapy in late-stage clinical development for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), a rare connective tissue disorder without an approved therapy. Treatment with EB-101 involves using gene transfer to deliver COL7A1 genes into a patients own skin cells (keratinocytes and its progenitors) and transplanting them back to the patient to enable normal Type VII collagen expression and facilitate wound healing. Data from a Phase I/IIa clinical trial conducted by Stanford University evaluating EB-101 showed that the gene-corrected cell therapy provided durable wound healing for RDEB patients lasting 2+ to 5+ years, including for the largest, most challenging wounds that affect the majority of the RDEB population. In the U.S., Abeona holds Regenerative Medicine Advanced Therapy, Breakthrough Therapy, and Rare Pediatric designations for EB-101 and Orphan Drug designation in both the U.S. and EU.

About Recessive Dystrophic Epidermolysis BullosaRecessive dystrophic epidermolysis bullosa (RDEB) is a rare connective tissue disorder characterized by severe skin wounds that cause pain and can lead to systemic complications impacting the length and quality of life. People with RDEB have a defect in the COL7A1 gene, leaving them unable to produce functioning Type VII collagen which is necessary to anchor the dermal and epidermal layers of the skin. There is currently no approved treatment for RDEB.

About Abeona Therapeutics Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing gene and cell therapies for serious diseases. The Companys clinical programs include EB-101, its autologous, gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa, as well as ABO-102 and ABO-101, novel AAV9-based gene therapies for Sanfilippo syndrome types A and B (MPS IIIA and MPS IIIB), respectively. The Companys portfolio of AAV9-based gene therapies also features ABO-202 and ABO-201 for CLN1 disease and CLN3 disease, respectively. Abeona has received numerous regulatory designations from the FDA and EMA for its pipeline candidates, including Regenerative Medicine Advanced Therapy designation for two candidates (EB-101 and ABO-102). http://www.abeonatherapeutics.com

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Forward Looking StatementThis press release contains certain statements that are forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and that involve risks and uncertainties. These statements include statements about the Companys clinical trials, including the timing and success thereof; the Companys products and product candidates; EB-101 can provide durable healing in large, chronic wounds that afflict many RDEB patients; future regulatory interactions with regulatory authorities; and the Companys goals and objectives. We have attempted to identify forward-looking statements by such terminology as may, will, believe, estimate, expect, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances), which constitute and are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, numerous risks and uncertainties, including but not limited to continued interest in our rare disease portfolio, our ability to enroll patients in clinical trials, the outcome of any future meetings with the U.S. Food and Drug Administration or other regulatory agencies, the impact of competition, the ability to secure licenses for any technology that may be necessary to commercialize our products, the ability to achieve or obtain necessary regulatory approvals, the impact of changes in the financial markets and global economic conditions, risks associated with data analysis and reporting, and other risks as may be detailed from time to time in the Companys Annual Reports on Form 10-K and quarterly reports on Form 10-Q and other periodic reports filed by the Company with the Securities and Exchange Commission. The Company undertakes no obligation to revise these forward-looking statements or update them to reflect events or circumstances occurring after the date of this presentation, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws.

Investor Contact:Dan FerryLifeSci Advisors, LLC+1 (617) 535-7746daniel@lifesciadvisors.com

Media Contact:Scott SantiamoDirector, Corporate CommunicationsAbeona Therapeutics+1 (718) 344-5843ssantiamo@abeonatherapeutics.com

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Abeona Therapeutics Announces First Patient Treated in Pivotal Phase III Clinical Trial Evaluating EB-101 Gene Therapy for Recessive Dystrophic...

The Associated Press visited a new intensive care ward in Brescia, one of the hardest-hit provinces in Lombardy. Dr. Sergio Cattaneo, the hospitals head of anesthesiology and intensive care, says hes seen many changes to fight the pandemic. (March 18) AP Domestic

Various claims thatItalians over the age of 80 would be "left to die" have surfaced within the past week on social media, with some posts saying the blame falls on Italy's socialized health care system.

Italy's COVID-19 fatality rate of 5% is higher than the global average of 3.5%. As the country's confirmed cases continue to surge, health officials are scrambling to find adequate resources.

Despite a countrywide lockdown,Italy reached a grave milestone this week when the country's death tollsurpassed China's as of March 19,3,405 people have died.

Italy has an older population,with a median age of 47.3, compared to 38.3 in the United States. Older populations are much more susceptible to complications from COVID-19, and many of the reported deaths in Italy have been people in their 80s and 90s.

The claims of Italy abandoning its elderly population began to surface following a report in the Telegraph about a document prepared by a crisis management unit in Turin, a northern Italiancity hit hard by the virus.

A man wearing a mask rides a scooter in Milan, Italy, March 11, 2020. Italy is mulling even tighter restrictions on daily life and has announced billions in financial relief to cushion economic shocks from the coronavirus. (Photo: Luca Bruno, AP)

The document seen by the Telegraph is a guideline for if and when it"becomes impossible to provide all patients with intensive care service,according to the news outlet, which did not publish a copy of it.

If the crisis reaches a point where health careaccess is too strained and needs to be limited, the document lays out plans for how to prioritize patients.

According to the Telegraph, the document's criteria for intensive therapy in emergency cases includes an age of less than 80 or a score of less than five on the Charlson Comorbidity Index, which indicates a patient's other medical conditions and mortality.

Luigi Icardi, a councilor for health in Piedmont, told the Telegraph he never wants the crisis to reach this point but the document "will be binding and will establish, in the event of saturation of the wards, a precedence code for access to intensive care, based on certain parameters such as potential survival."

Italy surpasses China in deaths.(Photo: USA TODAY)

Despite the tentative guidelines in the document, it is not true that Italy as a whole has decided not to treat their elderly for the coronavirus.

The truth is, instead, overwhelmed Italian health officials are planning for the worst, given the recent influx of cases and lack of available resources. If cases continue to surge, officials might be forced to prioritize care for those with "the best chance of success" and the "best hope of life."

The second part of theclaim that stemmed from the Telegraphreport blamed Italy's socialized health care for the lack of available resources and went viral on Facebook.

One person who posted that claim and had it go viral, Gene Ballinger,did not respond to request for comment by the time of publication.

Throughout the pandemic, Italy's Prime Minister Giuseppe Contehas remained consistent on his health care promises for all Italians.

"We live in a system in which we guarantee health and the right of everyone to be cured. It's a foundation, a pillar, and I'd say a characteristic of our system of civilization," Conte said in a public statement on March 9. "And thus, we can't allow ourselves to let our guard down."

Health care officials in China were faced with a similar dilemma when the number of cases surpassed the capability of the existing treatment options. As hospitals in China became overwhelmed, patients were forced to wait extended periods of time for treatment.

In the U.S., health care is not socialized.But officials across the country are preparing to facethe same dilemma seen in Italy as cases continue to multiply and available resources deplete.

A new Harvard analysis reveals many hospitals throughout the United States will not have enough beds for patients if the virus continues to spread and capacity is not adequately expanded.

According to the analysis, in 40% of marketsaround the country, hospitals will not be able to make enough room for all patients who fall ill from the coronavirus.

Medical staff work at one of the emergency structures that were set up to ease procedures at the Brescia hospital in northern Italy, March 16, 2020.(Photo: Luca Bruno, AP)

This statistic reflects a "moderate" scenario by the analysis team's standards andassumes 40% of adults will become infected with the virus over the next 12 months.

These numbers are not exact and do not take into account various efforts from hospitals across the country including sending home patients with less critical conditions.

The global push for social distancing, self-isolation and self-quarantine is a preemptive effort to prevent overwhelming healthcare systems.

The longer the disease takes to spread, the more time hospitals have to accommodate patients. In the United States, officials are attempting to "flatten the curve" and not overwhelm the health care system by closing businesses and schools and cancelling large events.

Blaming Italy's socialized health care system for the lack of availableresources doesn't hold up because nonsocialized health care systems, like those in the United States, are facing similarshortages.

While some Italian health officials are planning for the worst, the health care prioritizationguidelines have not yet been implemented and are influenced bymultiple factors including age, preexisting conditions and available resources. Forthe second claim about socialized health care,Italy's system has become overwhelmed due to the sheer amount of cases and patients, not because of its design. We rate these claims as FALSE, based on our research.

However, should Italy implement its protocol that triages patients based on age and other conditions, we would change the rating of these claims to PARTLY FALSE.

Read or Share this story: https://www.usatoday.com/story/news/factcheck/2020/03/20/fact-check-were-italians-left-die-socialized-medicine-blame-coronavirus/2887743001/

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Fact check: Were elderly Italians left to die? And is socialized health care to blame? - USA TODAY

Above: A researcher works in a lab that is developing testing for the COVID-19 coronavirus at Hackensack Meridian Health Center for Discovery and Innovation on February 28, 2020 in Nutley, New Jersey. (Photo by Kena Betancur/Getty Images)

There's a massive shortage of COVID-19 (Coronavirus) test kits in the U.S., as cases continue to skyrocket in places like Seattle and New York City. This is largely due to the failure of the Centers for Disease Control and Prevention (CDC) to distribute the tests in a timely fashion.

But it didn't have to be this way. Back in January and Februarywhen cases of the deadly disease began aggressively circulating outside of Chinadiagnostics already existed in places like Wuhan, where the pandemic began. Those tests followed World Health Organization (WHO) test guidelines, which the U.S. decided to eschew.

Instead, the CDC created its own in-depth diagnostics that could identify not only COVID-19, but a host of SARS-like coronaviruses. Then, disaster struck: When the CDC sent tests to labs during the first week of February, those labs discovered that while the kits did detect COVID-19, they also produced false positives when checking for other viruses. As the CDC went back to the drawing board to develop yet more tests, precious time ticked away.

"I think that we should have had testing more widely available about a month earlier," Dr. Carl Fichtenbaum, professor of clinical medicine at the University of Cincinnati's School of Medicine, tells Popular Mechanics. "That would have been more appropriate so that we could have identified people earlier on and used some of the mitigating strategies that were using now."

As the spread of Coronavirus continues to escalate in the U.S., private institutions like academic research hospitals are scrambling in a mad dash to come up with more test kits. And there is hope: the first human clinical trials for a possible vaccine have begun today.

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Testing for COVID-19 comes in two primary forms: You'll either have your throat swabbed if you're in the U.S., or perhaps have your blood drawn if you're in another country, like China. The different approaches ultimately come down to how scientists have developed the lab tests.

In the U.S., the CDC's diagnostic tool relies on polymerase chain reaction testing (PCR), which detects genetic material found in the virus's RNA. Unlike in other methods, the virus doesn't have to be alive for its presence to be detected.

"We take parts of the virus and we [test] whats called the conserved parts of the virus, parts that dont change a lot," Dr. Fichtenbaum explains. "There are always mutations. Were looking at the genetic code and we take a sequence of what we call primers, or things that will match up with that genetic code, and we put them through a series of steps where the primers will match the genetic code if [the virus] is present."

PCR testing is generally too advanced to be done at a hospital, and is more in the wheelhouse of clinical laboratory settings. There, researchers extract the sample's nucleic acidone of the four bases found in DNA sequencesto study the virus genome. They can amplify portions of that genome through a special process called reverse transcription polymerase chain reaction. That way, scientists can compare the sample to SARS-CoV-2, the virus that causes the novel coronavirus.

SARS-CoV-2 has almost 30,000 nucleotides in total, which make up its DNA. The University of Washington School of Medicine's PCR test hones in on about 100 of those that are known to be unique to the virus.

The researchers are looking for two genes in particular, and if they find both, the test is considered positive. If they only find one, the test is inconclusive. However, the CDC notes, "it is possible the virus will not be detected" in the early stages of the viral infection.

In some cases, Dr. Fichtenbaum says, it's possible to quantify the number of copies of the viral gene present. It could be one, 10, or 10 million, he says, and the higher that amount is, the more contagious you may be, or the further along you may be in the illness.

U.S. Centers for Disease Control and Prevention

As of press time, the CDC has directly examined some 4,069 specimens in Atlanta, according to data produced on Monday afternoon, while public health laboratories across the country have tested another 18,644. Notably, some data after March 11 is still pending.

Regardless, with about 1,600 confirmed cases in the U.S., those figures suggest roughly one in 13 people tested have actually contracted the novel Coronavirus. Surely, if more tests were available, those numbers would be higher, Dr. Fichtenbaum says. Because of the CDC snafu and an initial muted reaction to the outbreak from President Trump's administration, we're about a month behind on the diagnostics front, he adds.

Piling onto other reasons, Dr. Karen C. Carrolldirector of the Division of Medical Microbiology at Johns Hopkins University School of Medicinebelieves that the test shortage is "complicated" by the fact that no one expected COVID-19 to spread so quickly in the U.S.

Not to mention, manufacturers are now low on supplies that academic labs, like hers, require to develop and distribute test kits, she tells Popular Mechanics.

During a Congressional hearing on Wednesday, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the public health care system is failing to make tests available to people who may have contracted COVID-19.

"The idea of anybody getting [the test] easily the way people in other countries are doing it, we're not set up for that. Do I think we should be? Yes, but we're not," he said.

The silver lining: The CDC is now working in tandem with private labs to make more tests available. The concern then becomes how many tests these labs can actually perform each day. Experts estimate that most labs will have the capacity to complete about 100 tests per day, which just isn't good enough to contain COVID-19 at this point.

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Just because your doctor may have ordered you a COVID-19 test, that doesn't mean you'll actually receive one.

According to CDC guidelines, there are three general classes of patients who seek the diagnostic test, and it's up to the discretion of the health care systems to administer them. With limited supply, those are tough decisions. The classes are:

Testing can be quite restrictive, and people who aren't in a high risk category, or who have traveled to a country where there are cases of COVID-19but had no known exposure to the virusare turned away.

"Once we relax the standards for testing so that we can test on anyone we think appropriate, and its not as complicated, we'll be able to reduce the spread," Dr. Fichtenbaum says.

Right now in Ohio, where Dr. Fichtenbaum is based, doctors must fill out a four-page form and conduct in-depth tracing of a patient's movements before they can administer a test, he says. Not only is it time-consuming, but it may result in the patient not receiving a test at alland could have contracted the virus.

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To expedite the availability of diagnostics, the U.S. Food and Drug Administration (FDA) announced in late February that academic hospital systems had the green light to develop their own test kits.

The move allows these institutions to rely on their own internal validation upfront, rather than wait on the time-consuming FDA approvals process before using the tests. While FDA approval is still ultimately required under this policy, once the hospitals themselves have determined the tests are accurate and safe, they can begin using them.

Dr. Carroll of Johns Hopkins says that her lab went live with their own test yesterday. "Now, we have 15 days to send [the FDA] our validation package," she says. Her lab can now use the test to check for COVID-19 in patients that come to the medical center, but a few more things must also happen in tandem to satisfy the FDA's requirements.

Once a private lab sends in their validation package, which includes data collected during the test development, the FDA may call back with questions about the kit or ask for clarification. If the labs get radio silence for a while, that's normal, according to Dr. Carroll, but eventually, they must be granted what is known as an Emergency Use Authorization.

Under section 564 of the Federal Food, Drug, and Cosmetic Act, the FDA Commissioner may allow unapproved medical productslike privately developed COVID-19 teststo be used in an emergency for diagnosis, treatment or prevention when there are no better alternatives.

"I dont know how quickly they will get back to laboratories, they havent told us that," Dr. Carroll says.

Labs must also have close communication with their state health department laboratory, which is essentially the top lab in the state, she added. The FDA is requiring private institutions to send their first five negative and first five positive testing results to their state lab to ensure uniformity and effectiveness.

"A public health laboratory monitors certain communicable diseases," Dr. Carroll explains. "Some even offer testing for the community, like STDs such as Gonorrhea."

Other hospitals across the U.S. are making strides in test development, too. In Washington, where the CDC's faulty tests stymied the progress of testing, potentially aiding the community spread seen there, the University of Washington Medical Center has developed a COVID-19 test based on WHO recommendations, unlike the CDC. The hospital system has the capacity to conduct about 1,000 tests per day, and is working to ramp that up to 4,000 or 5,000 daily tests.

The Cleveland Clinic's test, meanwhile, should only take about eight hours to turn around a positive or negative result and should be ready by the end of March.

In a statement provided Thursday to Popular Mechanics, the Cleveland Clinic says it will soon have the capabilities to conduct on-site testing. "We are in the process of validating our testing capabilities and will soon send out more information."

Moving forward, Dr. Fichtenbaum expects the FDA to soon approve what's known as multiplex testing, which will allow labs to run 96 tests at once, rather than work with one specimen at a time.

"They need to approve that at each lab and theyre slow," says Dr. Fichtenbaum. But he anticipates the FDA will give the all-clear in the next few days. Then, it's just a matter of manufacturing the tests, which should happen rapidly.

Sparking some hope, the first participant in a human clinical trial for a COVID-19 vaccine will receive the first experimental dose on Monday, an unnamed government official told the Associated Press.

The trial is taking place at the Kaiser Permanente Washington Health Research Institute in Seattle. Testing will eventually include 45 young, healthy volunteers who will each be given different doses of shots developed by the National Institutes of Health and Moderna, Inc., a Cambridge, Massachusetts-based drug discovery and development firm. The shots will not include the virus, itself, so there is no chance of the participants contracting the virus. The goal is simply to check for unexpected side effects. It will take at least 12 to 18 months for any potential vaccine to be validated and made available to the public, public health officials say.

In the meantime, community spread continues, despite self-quarantine measures, countless canceled events, and sweeping work-from-home policies. The number of positive cases is probably significantly higher than the data shows, says Dr. Fichtenbaum, which only worsens the contagion.

"I think that COVID-19 is probably more prevalent in our communities than we think," he says.

And the clinical microbiologists working tirelessly at the front lines in hospitals fully expect to meet testing demand. Dr. Heba Mostafa, assistant professor of pathology at Johns Hopkins University, tells Popular Mechanics that she expects to see testing ramp up and really meet demand over the course of the next four to eight weeks.

And Dr. Carroll says that the spirit of collaboration between academic medical centers has been refreshing. The University of Texas and the University of Washington have each helped out the Johns Hopkins effort, she says. They helped supply the genetic material necessary to complete their test's validation. Still, it's grueling.

"Our hospital is very happy that we went live yesterday, but of course now theyre interested in how many tests we can do," Carroll said with a laugh. "I sometimes feel that clinical microbiologists are the unsung heroes."

March 16, 2020: This story has been updated to reflect the beginning of human clinical trials for a possible Covid-19 vaccine. The number of Covid-19 tests distributed and taken in the U.S. has also been updated.

Originally posted here:
Why There Aren't Enough Coronavirus Tests in the U.S. - Popular Mechanics

RESEARCH TRIANGLE PARK, N.C. and CHAPEL HILL, N.C., March 18, 2020 (GLOBE NEWSWIRE) -- Asklepios BioPharmaceutical, Inc. (AskBio), a leading clinical-stage adeno-associated virus (AAV) gene therapy company, today announced that it has entered into a research collaboration and licensing agreement with the University of North Carolina at Chapel Hill (UNC) for the development and commercialization of gene therapy for Angelman syndrome.

This collaboration allows us to leverage groundbreaking research from UNC and apply our AAV development capabilities to find a gene therapy treatment for Angelman syndrome, said Sheila Mikhail, JD, MBA, AskBio Chief Executive Officer and co-founder. We look forward to advancing this program together.

Angelman syndrome is a rare neurogenetic disorder caused by the loss of function of the UBE3A gene. The disorder occurs in approximately one in 15,000 people, or about 500,000 individuals worldwide, and there is currently no cure. In addition to life-altering symptoms such as speech and motor deficits, more than 80 percent of Angelman syndrome patients experience epilepsy, which typically does not respond well to standard anti-seizure medications.

A UNC School of Medicine team, led by Mark Zylka, PhD, and Ben Philpot, PhD, has generated preclinical evidence that gene therapy may help individuals with Angelman syndrome by improving seizure and motor outcomes.

Individuals with Angelman syndrome face lifelong challenges, and our gene therapy approaches hold the potential to correct this disorder at its genetic roots. We are incredibly excited to partner with AskBio, as they have been vanguards of clinical gene therapies for rare diseases, said Mark Zylka, PhD, Director of the UNC Neuroscience Center. Ben Philpot, PhD, Associate Director of the UNC Neuroscience Center added, We look forward to advancing this transformative treatment to the clinic and potentially improving the lives of individuals with Angelman syndrome.

The partnership between AskBio and UNC could transform the lives of people living with Angelman syndrome by providing them with a potential therapy for this rare disease, said Amanda Moore, Angelman Syndrome Foundation CEO. The Angelman Syndrome Foundation has long been proud to support the work of UNC researchers, Drs. Ben Philpot and Mark Zylka, and invest in science that positively affects the Angelman syndrome community. The collaboration between UNC and AskBio brings us a step closer to delivering a viable gene therapy to the people and families we serve.

The financial terms of the agreement were not disclosed.

More about Angelman SyndromeDeletion of the maternally inherited copy of the UBE3A gene causes Angelman syndrome. Symptoms include microcephaly (small head circumference), severe intellectual disability, seizures, balance and movement problems (ataxia), lack of speech, and sleep problems. Behavioral symptoms include frequent laughing, smiling and excitability. Angelman syndrome was first described in 1965, yet no treatment options have been approved in the 55 years since. While individuals with the disorder have a normal lifespan, they require life-long care and are not able to live independently.

About Angelman Syndrome FoundationThe mission of the Angelman Syndrome Foundation is to advance the awareness and treatment of Angelman syndrome through education and information, research and support for individuals with Angelman syndrome, their families and other concerned parties. We exist to give them a reason to smile, with the ultimate goal of finding a cure. To learn more, visit https://www.angelman.org.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process called Pro10 and an extensive adeno-associated virus (AAV) capsid and promoter library. Based in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. AskBio maintains a portfolio of clinical programs across a range of neurodegenerative and neuromuscular indications with a current clinical pipeline that includes therapeutics for Pompe disease, limb-girdle muscular dystrophy 2i/R9 and congestive heart failure, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). Learn more at https://www.askbio.com or follow us on LinkedIn.

Media Contacts: AskBio Robin Fastenau Vice President, Communications +1 984.275.2705 rfastenau@askbio.com Angelman Syndrome Foundation Amanda Moore Chief Executive Officer +1 317.514.6918 amoore@angelman.org UNC Health | UNC School of Medicine Mark Derewicz Director, Research & News +1 984.974.1915 Mark.Derewicz@unchealth.unc.edu

Continued here:
AskBio Enters Research Collaboration and Licensing Agreement with University of North Carolina (UNC) for Angelman Syndrome - Associated Press

Scientists at the Casey Eye Institute, in Portland, Ore., have have injected a harmless virus containing CRISPR gene-editing instructions inside the retinal cells of a patient with a rare form of genetic blindness. KTSDesign/Science Photo Library/Getty Images hide caption

Scientists at the Casey Eye Institute, in Portland, Ore., have have injected a harmless virus containing CRISPR gene-editing instructions inside the retinal cells of a patient with a rare form of genetic blindness.

For the first time, scientists have used the gene-editing technique CRISPR to try to edit a gene while the DNA is still inside a person's body.

The groundbreaking procedure involved injecting the microscopic gene-editing tool into the eye of a patient blinded by a rare genetic disorder, in hopes of enabling the volunteer to see. They hope to know within weeks whether the approach is working and, if so, to know within two or three months how much vision will be restored.

"We're really excited about this," says Dr. Eric Pierce, a professor of ophthalmology at Harvard Medical School and director of the Inherited Retinal Disorders Service at Massachusetts Eye and Ear. Pierce is leading a study that the procedure launched.

"We're helping open, potentially, an era of gene-editing for therapeutic use that could have impact in many aspects of medicine," Pierce tells NPR.

The CRISPR gene-editing technique has been revolutionizing scientific research by making it much easier to rewrite the genetic code. It's also raising high hopes of curing many diseases.

Before this step, doctors had only used CRISPR to try to treat a small number of patients who have cancer, or the rare blood disorders sickle cell anemia or beta-thalassemia. While some of the initial results have been promising, it's still too soon to know whether the strategy is working.

In those other cases, doctors removed cells from patients' bodies, edited genes in the cells with CRISPR in the lab and then infused the modified cells back into the volunteers' bodies to either attack their cancer or produce a protein their bodies are missing.

In this new experiment, doctors at the Casey Eye Institute in Portland, Ore., injected (into the eye of a patient who is nearly blind from a condition called Leber congenital amaurosis) microscopic droplets carrying a harmless virus that had been engineered to deliver the instructions to manufacture the CRISPR gene-editing machinery.

Beginning in infancy, the rare genetic condition progressively destroys light-sensing cells in the retina that are necessary for vision. Vision impairment with LCA varies widely, but most patients are legally blind and are only able to differentiate between light and dark or perhaps to detect movement.

"The majority of people affected by this disease have the most severe end of the spectrum, in terms of how poor their vision is," Pierce says. "They're functionally blind."

The goal is that once the virus carrying the CRISPR instructions has been infused into the eye, the gene-editing tool will slice out the genetic defect that caused the blindness. That would, the researchers hope, restore production of a crucial protein and prevent the death of cells in the retina, as well as revive other cells enabling patients to regain at least some vision.

"It's the first time the CRISPR gene-editing is used directly in a patient," Pierce says. "We're really optimistic that this has a good chance of being effective."

The study is being sponsored by Editas Medicine, of Cambridge, Mass., and Allergan, based in Dublin. It will eventually involve a total of 18 patients, including some as young as ages 3 to 17, who will receive three different doses.

"We're very excited about this. This is the first time we're doing editing inside the body," says Charles Albright, the chief scientific officer at Editas.

"We believe that the ability to edit inside the body is going to open entire new areas of medicine and lead to a whole new class of therapies for diseases that are not treatable any other way," Albright says.

Francis Collins, director of the National Institutes of Health, calls the advance "a significant moment."

"All of us dream that a time might be coming where we could apply this approach for thousands of diseases," Collins tells NPR. "This is the first time that's being tried in a human being. And it gives us hope that we could extend that to lots of other diseases if it works and if it's safe."

Pierce, Albright and others stressed that only one patient has been treated so far and that the study, still at a very early stage, is designed primarily to determine whether injecting the gene-editing tool directly into the eye is safe.

To that end, the researchers are starting with lowest dose and the oldest patients, who have already suffered extensive damage to their vision. And doctors are only treating one eye in each patient. All of those steps are being taken in case the treatment somehow backfires, causing more damage instead of being helpful.

"CRISPR has never been used directly inside a patient before," Pierce says. "We want to make sure we're doing it right."

Still, he says, if the underlying defect can be repaired in this patient and others with advanced damage, "we have the potential to restore vision to people who never had normal vision before. It would indeed be amazing."

The study involves a form of Leber congenital amaurosis known as Type 10, which is caused by a defect in the CEP290 gene.

If the approach appears to be safe and effective, the researchers will start treating younger patients.

"We believe children have the potential to have the most benefit from their therapy, because we know their visual pathways are still intact," Albright explains.

The procedure, which takes about an hour to perform, involves making tiny incisions that enable access to the back of the eye. That allows a surgeon to inject three droplets of fluid containing billions of copies of the virus that has been engineered to carry the CRISPR gene-editing instructions under the retina.

The idea is that once there, the CRISPR editing elements would snip out the mutation that causes a defect in CEP290. The hope is that this would be a one-time treatment that would correct vision for a lifetime.

If it works, the volunteers in the study might be able to have the procedure repeated on the other eye later.

"If we can do this safely, that opens the possibility to treat many other diseases where it's not possible to remove the cells from the body and do the treatment outside," Pierce says.

The list of such conditions might include some brain disorders, such Huntington's disease and inherited forms of dementia, as well as muscle diseases, such as muscular dystrophy and myotonic dystrophy, according to Pierce and Albright.

"Inherited retinal diseases are a good choice in terms of gene-based therapies," says Artur Cideciyan, a professor of ophthalmology at the University of Pennsylvania, given that the retina is easily accessible.

But Cideciyan cautions that other approaches for these conditions are also showing promise, and it remains unclear which will turn out to be the best.

"The gene-editing approach is hypothesized to be a 'forever fix,' " he says. "However, that's not known. And the data will have to be evaluated to see the durability of that. We'll have to see what happens."

Originally posted here:
CRISPR Used To Edit Genes Inside A Patient With A Rare Form Of Blindness : Shots - Health News - NPR

The number of people treated with approved gene therapies and gene-modified cell therapies like CAR-T cancer treatments in the United States and Europe has reached more than 4,500, according to an estimate from the Alliance for Regenerative Medicine.

The figure comes from the trade groups 2019 annual report, released Thursday. The alliance also reported that 1,066 clinical trials for gene therapies, cell therapies, and tissue engineering products were underway at the end of 2019. Regenerative medicine trials have room for more than 60,000 patients to enroll around the world.

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Gene and cell therapies continue growth in patients, financing, and costs - STAT

The global market for precision medicine is projected to top more than $84.5 billion by 2024. Targeted therapies for rare, genetic diseases, cancer and chronic conditions come with the hope of a cure.

Companies such as Roche, Novartis, Spark Therapeutics (now owned by Roche), Pfizer, Editas Medicine, and BioMarin Pharmaceuticals are among the pharma players in this space. There seem to be new developments in precision medicine on almost a weekly basis.

So what do educational institutions need to do to create fertile ground for gene therapy research to produce the next generation of companies developing these therapies? And what needs to happen to facilitate data sharing, ensure access to genome sequencing and these promising therapies?

A new eBook highlights compelling conversations around a couple of events that took place during the JP Morgan Healthcare conference in January this year. One, hosted by the Penn Center for Innovation, offers a showcase of the latest biotech innovations emerging from Penn and the Perelman School of Medicine. Another, hosted by Deloitte and P4ML, drew attention to an initiative by the World Economic Forum to improve the way genomic data is shared to develop better treatments for rare diseases and ethical considerations for access to precision medicine.

Fill in the form below to download the eBook, The Pathway to Precision Medicine.

See more here:
A snapshot of the precision medicine landscape - MedCity News