Cep290

FRIDAY, Sept. 6, 2024 -- Gene therapy may restore vision to children and adults robbed of their sight by a rare inherited condition called Leber congenital amaurosis, researchers report. The illness is caused by mutations in the GUCY2D gene, which is critical to producing proteins that enable vision. People with this form of Leber congenital amaurosis (LCA1) typically lose their vision in early childhood. Just under 100,000 people are thought to be affected worldwide. However, a team of researchers at the University of Pennsylvania say that a new gene therapy injected under the retinas of children and adults with LCA1 improved vision by 100 to 10,000 times. “Even though we previously predicted a large vision improvement potential in LCA1, we did not know how receptive patients’ [eye] photoreceptors would be to treatment after decades of blindness,” noted study co-lead author Artur Cideciyan , a research professor of ophthalmology at the university. “It is very satisfying to see a successful multi-center trial that shows gene therapy can be dramatically efficacious.” The findings were published Sept. 5 in The Lancet journal. A total of 15 LCA1 patients -- 12 adults and three children -- participated in the new trial. All had vision that was equal to or below 20/80, meaning that objects a normally sighted person could see at 80 feet could only be clear at 20 feet away for a person with LCA1. Glasses were of little help, because glasses only address the eye's focusing ability, not any underlying medical cause driving vision loss. The new gene therapy is called ATSN-101 and was developed by Atsena Therapeutics, which funded the new trial. This was a small phase 2 trial, meant to gauge a treatment's safety and explore differences when various dosages are used. The injected therapy was tried at three different dosages. Three adult patients each received low, medium and high doses of ATSN-101. Once the treatments' safety was assessed, six participants (including the three children) received high-dose ATSN-101. According to the research team, vision began to improve quickly in all patients, usually within a month of treatment. Improvements have lasted for at least a year. Patients' vision was tested in various ways, including their ability to move through a sometimes dimly-lit pathway, eye charts and "light flash" tests conducted in a dark environment. Two of nine patients who got the high-dose treatment had a 10,000-fold improvement in their sight, Cideciyan's group reported. “That 10,000-fold improvement is the same as a patient being able to see their surroundings on a moonlit night outdoors as opposed to requiring bright indoor lighting before treatment,” said Cideciyan, who also co-directs the Center for Hereditary Retinal Degenerations at UPenn. “One patient reported for the first time being able to navigate at midnight outdoors only with the light of a bonfire.” Side effects could happen, and were usually related to the surgery used to implant the gene therapy. These included tiny hemorrhages within the eye that later healed, or transient inflammation of the eye, treated with steroids. The patients' vision is being tracked going forward, the researchers said, and a bigger, randomized trial is being planned as a requirement of any U.S. Food and Drug Administration approval of the new therapy. The new work follows on the team's prior success using gene therapy to reverse another form of Leber congenital amaurosis, this time connected to a mutation in the CEP290 gene. “The treatment success in our most recent clinical trials together with our earlier experience brings hope for a viable treatment for about 20 percent of infantile blindness caused by inherited retinal degenerations,” study co-author Dr. Tomas Aleman said in a UPenn news release. He is research professor in ophthalmology and co-director of the Center for Hereditary Retinal Degenerations. “The focus now is on perfecting the treatments and treating earlier manifestations of these conditions once safety is confirmed," he said. "We hope similar approaches will lead to equally positive outcomes in other forms of congenital retinal blindness.” Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

About 79% of clinical trial participants experienced measurable improvement after receiving experimental, CRISPR-based gene editing that is designed to fix a rare form of blindness, according to a new article. About 79% of clinical trial participants experienced measurable improvement after receiving experimental, CRISPR-based gene editing that is designed to fix a rare form of blindness, according to a paper published today in the New England Journal of Medicine. "This trial shows CRISPR gene editing has exciting potential to treat inherited retinal degeneration," said Mark Pennesi, M.D., Ph.D., a corresponding author on the paper, an ophthalmologist and Oregon Health & Science University's lead scientist for the Phase 1/2 BRILLIANCE trial. "There is nothing more rewarding to a physician than hearing a patient describe how their vision has improved after a treatment. One of our trial participants has shared several examples, including being able to find their phone after misplacing it and knowing that their coffee machine is working by seeing its small lights. "While these types of tasks might seem trivial to those who are normally sighted, such improvements can have a huge impact on quality of life for those with low vision." The BRILLIANCE trial evaluated the safety and effectiveness of EDIT-101, an experimental gene editing treatment developed by Editas Medicine that uses CRISPR technology. The experimental treatment was designed to edit a mutation in the CEP290 gene, which provides instructions to create a protein that is critical for sight. People with this gene mutation have a rare condition that is commonly called Leber Congenital Amaurosis, or LCA, Type 10, for which there is currently no Food and Drug Administration-approved treatment. LCA's various types occur in about 2 or 3 out of 100,000 newborns. The OHSU Casey Eye Institute treated the trial's first participant in early 2020. That procedure also marked the first time that CRISPR had been used to edit genes within the human body, called in vivo gene editing. The new paper describes the study's findings through February 2023 and details how the trial's 14 participants -- 12 adults and two children -- responded to receiving EDIT-101 in one eye. Key results include: Four specific outcomes were used to evaluate the experimental treatment's effectiveness: Further research for a future treatment In November 2022, trial sponsor Editas Medicine announced that it was pausing the trial's enrollment and would seek another partner to continue the experimental therapy's development. Pennesi and colleagues are exploring working with other commercial partners to conduct additional trials, in collaboration with Editas. The researchers hope future studies can examine ideal dosing, whether a treatment effect is more pronounced in certain age groups such as younger patients, and include refined endpoints to measure impacts on activities of daily living. "This research demonstrates that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials," said Mass Eye & Ear ophthalmologist Eric Pierce, M.D., Ph.D., who is also a corresponding author. "While more research is needed to determine who may benefit most, we consider the early results promising. To hear from several participants how thrilled they were that they could finally see the food on their plates -- that is a big deal. These were individuals who could not read any lines on an eye chart and who had no treatment options, which is the unfortunate reality for most people with inherited retinal disorders." "Our patients are the first congenitally blind children to be treated with gene editing, which significantly improved their daytime vision," said the paper's third corresponding author, Tomas S. Aleman, M.D., a pediatric ophthalmologist at the Children's Hospital of Philadelphia and the University of Pennsylvania's Scheie Eye Institute. "Our hope is that the study will pave the road for treatments of younger children with similar conditions and further improvements in vision. This trial represents a landmark in the treatment of genetic disease, in specific genetic blindness, by offering important alternative treatment when traditional forms of therapy, such as gene augmentation, are not an option." "The results from the BRILLIANCE trial provide proof of concept and important learnings for the development of new and innovative medicines for inherited retinal diseases. We've demonstrated that we can safely deliver a CRISPR-based gene editing therapeutic to the retina and have clinically meaningful outcomes," said Editas Medicine Chief Medical Officer Baisong Mei, M.D., Ph.D. The OHSU Casey Eye Institute is one of five clinical sites that recruited participants for the trial. The other sites are: Bascom Palmer Eye Institute in Miami, Florida; Mass Eye and Ear in Boston, Massachusetts; Scheie Eye Institute at the University of Pennsylvania and Children's Hospital of Philadelphia; and Kellogg Eye Center in Ann Arbor, Michigan.

MALVERN, Pa., Dec. 13, 2023 (GLOBE NEWSWIRE) -- Ocugen, Inc. (“Ocugen” or the “Company”) (NASDAQ: OCGN), a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies, biologics, and vaccines, today announced that the first patient has been dosed in the ArMaDa Phase 1/2 clinical trial of OCU410 (AAV-RORA), a modifier gene therapy product candidate being developed for dry AMD (dAMD). “OCU410, our first-in-class modifier gene therapy for dAMD, addresses gaps among other therapies available and in development for dAMD as a potential one-time treatment for life,” said Dr. Shankar Musunuri, Chairman, CEO and Co-Founder of Ocugen. “We are very pleased to continue advancing our ophthalmic gene therapy pipeline, which remains the Company’s primary focus.” This Phase 1/2 trial will assess the safety and efficacy of OCU410 for geographic atrophy (GA) secondary to dAMD and will be conducted in two phases. Phase 1 is a multicenter, open-label, dose-ranging study. Phase 2 is a randomized expansion phase in which subjects will be randomized in a 1:1:1 ratio to either one of two OCU410 dose groups or to an untreated control group. OCU410 is a potential curative therapy with a single sub-retinal injection that targets multiple pathways causing dAMD, including lipid metabolism, inflammation, oxidative stress, and complement activation. Currently, the other therapeutic options available target only complement activation and require approximately 6-12 intravitreal injections annually. “Breaking new ground in the pursuit of vision restoration, our pioneering modifier gene therapy candidate, OCU410, achieves another major milestone by dosing a GA patient in a Phase 1/2 clinical trial,” said Arun Upadhyay, PhD, Chief Scientific Officer, Head of R&D at Ocugen. “OCU410 offers hope for those battling GA that are faced with limited treatment options and the real prospect of ultimately losing their vision.” “There remains a great unmet need for novel durable and effective treatments for GA, which remains one of the most common causes of vision loss globally,” said Benjamin Bakall, MD, PhD, director of clinical research at Associated Retina Consultants (ARC) and clinical assistant professor at University of Arizona, College of Medicine – Phoenix. “I am excited that we performed the first surgery with this novel therapeutic approach—designed to restore homeostasis and slow disease progression following a single treatment—at ARC in Phoenix, AZ, with the surgical team led by Dr. Mark Kwong, medical director of ARC.” The first surgery was successful in delivering the new gene underneath the retina; the light sensitive nerve tissue lining the inside of the eye. About dAMD and GAdAMD affects approximately 10 million Americans and more than 266 million people worldwide. It is characterized by the thinning of the macula. The macula is the part of the retina responsible for clear vision in one’s direct line of sight. dAMD involves the slow deterioration of the retina with submacular drusen (small white or yellow dots on the retina), atrophy, loss of macular function and central vision impairment. dAMD accounts for 85-90% of the total AMD population. GA, an advanced form of dry age-related macular degeneration, affects approximately 1 million people in the United States alone. About OCU410OCU410 utilizes an AAV delivery platform for the retinal delivery of the RORA (RAR Related Orphan Receptor A) gene. The RORA protein plays an important role in lipid metabolism, reducing lipofuscin deposits and oxidative stress, and demonstrates an anti-inflammatory role in-vitro and in-vivo (animal model) studies. These results demonstrate the ability for OCU410 to target multiple pathways linked with dAMD pathophysiology. Ocugen is developing AAV-RORA as a one-time gene therapy for the treatment of GA. Currently, the other therapeutic options available target only complement activation and require approximately 6-12 intravitreal injections annually. About Ocugen, Inc.Ocugen, Inc. is a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies, biologics, and vaccines that improve health and offer hope for patients across the globe. We are making an impact on patient’s lives through courageous innovation—forging new scientific paths that harness our unique intellectual and human capital. Our breakthrough modifier gene therapy platform has the potential to treat multiple retinal diseases with a single product, and we are advancing research in infectious diseases to support public health and orthopedic diseases to address unmet medical needs. Discover more at www.ocugen.com and follow us on X and LinkedIn. About Associated Retina ConsultantsAssociated Retina Consultants is the largest independent retina practice in the state of Arizona, taking part in groundbreaking clinical trials to bring new treatments for the benefit of patients with diseases affecting the retina. In addition to collaborating with Ocugen on the OCU410 clinical trial, in October 2023, Associated Retina Consultants—with a surgical team led by Dr. Mark Kwong—performed gene therapy with OCU400 on a pediatric CEP290 patient. This was the first retinal gene therapy of its kind performed on a child in Arizona. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, which are subject to risks and uncertainties. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks, and uncertainties that may cause actual events or results to differ materially from our current expectations. These and other risks and uncertainties are more fully described in our periodic filings with the Securities and Exchange Commission (SEC), including the risk factors described in the section entitled “Risk Factors” in the quarterly and annual reports that we file with the SEC. Any forward-looking statements that we make in this press release speak only as of the date of this press release. Except as required by law, we assume no obligation to update forward-looking statements contained in this press release whether as a result of new information, future events, or otherwise, after the date of this press release. Contact:Tiffany HamiltonHead of CommunicationsIR@ocugen.com