I
n a Phase 3 gene therapy trial intended to improve vision among patients with Leber hereditary optic neuropathy, recipients gained somewhat better sight in both eyes even though only one was treated. The results and an investigation into possible explanations for the findings were published December 9 in Science Translational Medicine.
The paper has very strong clinical implications that a single injection maybe is enough for bilateral effects, says Thomas Corydon, who studies ocular gene therapy at Aarhaus University in Denmark and was not involved in the work.
The onset of Leber hereditary optic neuropathy (LHON) is sudden. Patientsusually young menstart losing vision at the center of one eye. Within months, the other eye follows, leaving them legally blind. The disease is caused by a point mutation in the mitochondrial genome that leads to dysfunction and death of retinal ganglion cells, the axons of which make up the optic nerve. About 70 percent of patients have the same mutation, known as MT-ND4.
If you're going to start somewhere, it makes sense to tackle this variant, says Patrick Yu-Wai-Man, an ophthalmologist at the University of Cambridge in the United Kingdom. He and his collaborators, including teams from GenSight Biologics and Stealth Biotherapeutics and a group led by University of Pittsburg Medical Center ophthalmologist Jos-Alain Sahel, as well as other groups, previously showed that the point mutation could be corrected in animal models and in cell culture using gene therapy.
Its difficult to get genetic material into the mitochondrial genome because mitochondria have two membranes, an outer and inner membrane, Yu-Wai-Man explains. In the clinical trial, he, Sahel, and colleagues overcame this hurdle by injecting an AAV vector containing a wildtype copy of the ND4gene with an added mitochondrial-targeting sequencea strategy that had already been shown to correctly direct the protein product of ND4 and other mitochondrial genes to the organelle.
Each of 37 patients received the therapeutic virus via a single injection into the fluid within one eye six to 12 months after the onset of vision loss. They also got a sham treatment in the other eye: a surgeon pressed the eye with a blunt cannula to simulate an injection.
We thought that, if there was going to be an effect, it would be isolated to that eye and then the other one would be the perfect internal control, Yu-Wai-Man tells The Scientist. But as it turns out, that wasnt the case.
With a slight delay in the sham-treated eye, both eyes started to improve. By 96 weeks after treatment, 29 of the patients had gained visual acuity in both eyes and reported increases in their quality of life.
Patients do improve, but, even with the treatment, they still function at a very low level, says Byron Lam, an ophthalmologist at the University of Miami who was not involved in the study. Most of the subjects were still near legal blindness at the end of the study.
To determine how the bilateral effect might be happening, Yu-Wai-Man and colleagues injected the therapeutic virus into one eye of three monkeys. Three months later, they found viral DNA in the noninjected eye and optic nerve. This raises the possibility that the viral vector supplies the wildtype protein in the untreated eye, but its not firm proof.
Finding viral DNA in the untreated eye in primates is a little short of being definitive because DNA expression alone doesnt prove that youre getting a therapeutic effect. Detecting DNA doesnt mean there is mRNA expression or protein production, says Mark Pennesi, an ophthalmologist at Oregon Health & Science University who did not participate in the work.
Previous work has shown that there could be transneuronal spread of the vector, but we also need to keep a critical mind and think that there might be other explanations, agrees Yu-Wai-Man. It could be that injecting the vector in one eye leads to some form of localized inflammation that induces mitochondrial biogenesis, thus making the mitochondria work better, he adds. Another option is that improvement in one eye leads to reorganization in the part of the brain that interprets signals from the eye, which could enhance vision overall.
Clearly, further investigations are needed to understand the underlying mechanisms of how the interocular diffusion of viral DNA vector occurs and whether there are other mechanisms by which the optic nerves directly communicate, Bin Li, an ophthalmologist at Tongji Hospital in China who was not involved in the study, writes in an email to The Scientist.Li explains that his group has also reported that material injected in one eye can reach the other optic nerve.
These findings have implications for how this type of research should be performed in the future, he writes. Theyve shown that contralateral sham-treated eyes cannot serve as true internal control for clinical studies.
When you read this paper, you get a little excited, and then in some ways, you get a little disappointed, because it does look like theres some kind of positive effect with this treatmentthat it does do something more than what would happen with just the natural history of the disease. Unfortunately, the results are confounded by the fact that you treat one eye, but then there is improvement in the untreated control eye, Pennisi tells The Scientist. The question then really becomes . . . why did you get that result?
Along with academic collaborators, Yu-Wai-Man, who consults for GenSight Biologics and Stealth Biotherapeutics, will continue to explore this question as they focus on ongoing clinical trials of this therapeutic.
P. Yu-Wai-Man et al., Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy,Science Translational Medicine,doi:10.1126/scitranslmed.aaz7423, 2020.
Continue reading here:
Gene Therapy in One Eye Improves Vision in Both Eyes - The Scientist
- Types of Blindness, Causes, and Their Treatment - Healthline - March 28th, 2025
- Types of blindness: Partial, total, congenital, and more - March 28th, 2025
- International collaborations helping understand the physical activity levels and well-being of children with visual impairment - Murdoch University - March 28th, 2025
- Revel in the Rainbow: Color-Blindness-Correcting Glasses Debut at Wooden Shoe Festival - Portland Monthly - March 28th, 2025
- Prevent Blindness Declares April as Women's Eye Health and Safety Month, Providing Free Educational Resources to the Public and Professionals - PR Web - March 28th, 2025
- Partial blindness hasn't stopped Oklahoma State's Stailee Heard from leading the Cowgirls into NCAAs - The Washington Post - March 28th, 2025
- Nine out of ten cases of blindness caused by glaucoma could be prevented through annual check-ups - Euro Weekly News - March 28th, 2025
- The silent sight thief: The devastating effects of glaucoma on mental health and quality of life - News24 - March 28th, 2025
- Rosie O'Donnell Celebrates Her 63rd Birthday After Move to Ireland as She Slams 'Willful Blindness' in Trump Administration - AOL - March 28th, 2025
- Partial blindness hasn't stopped Oklahoma State's Stailee Heard from leading the Cowgirls into NCAAs - Eagle-Tribune - March 28th, 2025
- The Longevity Wake-Up Call And The Blindness Of Leadership To It - Forbes - February 24th, 2025
- Album Review: Blindness // The Murder Capital - The Indiependent - February 24th, 2025
- The Murder Capital - Blindness - Northern Transmissions - February 24th, 2025
- The Murder Capital: Blindness review - independent pop | Indie - The Line of Best Fit - February 24th, 2025
- Prevent Blindness Kicks Off Second Annual "Retinopathy of Prematurity (ROP) Awareness Week," Feb. 24- March 2, 2025, as Part of its ROP... - February 24th, 2025
- Prevent Blindness Kicks Off Second Annual Retinopathy of Prematurity Awareness Week - Vision Monday - February 24th, 2025
- Gene therapy for rare childhood blindness shows lasting vision gains - R&D World - February 24th, 2025
- The Murder Capital's Blindness: A Voice of Significance in an Era Craving Authentic Discourse - Indie Is Not A Genre - February 24th, 2025
- Albums Of The Week: The Murder Capital | Blindness - Tinnitist - February 24th, 2025
- After Maine native testifies before Congress, Elon Musk targets his disability - Press Herald - February 24th, 2025
- Ozempic could BLIND you - it damages veins in the eye, major study finds - Daily Mail - February 24th, 2025
- Cerebral Venous Thrombosis Presenting With Binocular Blindness and Bilateral Sensorineural Hearing Loss - Cureus - February 24th, 2025
- Treatment for horses may lead to therapy for type of blindness - Mid Florida Newspapers - February 24th, 2025
- The Murder Capital: Blindness album review - Louder Than War - February 24th, 2025
- 'First in the world': London doctors cure blindness in children born with a genetic condition - WION - February 24th, 2025
- Doctors cure rare blindness in infants with gene therapy - NewsBytes - February 24th, 2025
- Gene therapy new trial treats rare blindness in children - Daily Jang - February 24th, 2025
- Ozempic Blindness Could Be Rare but Real: What Experts Say About the Risk - ZME Science - February 24th, 2025
- Parents of boy with rare eye condition hail amazing results of gene therapy - Yahoo News UK - February 24th, 2025
- Myths and Assumptions about Blindness - BBC.com - February 24th, 2025
- Man accused of beating victim, causing permanent blindness in one eye - KAIT - February 15th, 2025
- Scientists Find Link Between Weight Loss Drugs and Blindness - AOL - February 15th, 2025
- Treatment for horses may lead to therapy for type of blindness - University of Florida - February 15th, 2025
- How Ageism Impacts Adults with Low Vision - National Council on Aging - February 15th, 2025
- Ozempic and other weight loss drugs may be linked to conditions that could lead to blindness, study says - Quartz - February 15th, 2025
- Treatment for horses may lead to therapy for type of blindness - Phys.org - February 15th, 2025
- Treatment for Horses May Lead to Therapy for Type of Blindness - Morning Ag Clips - - February 15th, 2025
- Foundation Fighting Blindness Celebrates 20 Years of VisionWalk - PR Newswire - February 15th, 2025
- Woman Victim of 'Lash Blindness'Shock at How She Looks Without Them - Newsweek - February 15th, 2025
- Some Ozempic users are losing their vision - but scientists dont know why - The Independent - February 15th, 2025
- Those with visual impairments or blindness tackling the trails at Pico Mountain - WCAX - February 15th, 2025
- Prevent Blindness Issues Call for Nominations for the 2025 Jenny Pomeroy Award for Excellence in Vision and Public Health, and Rising Visionary Award... - February 15th, 2025
- Medical warning: Ozempic and Mounjaro may be linked to vision loss - India Today - February 15th, 2025
- New research links Ozempic to vision loss and risk of blindness - MSN - February 15th, 2025
- Ozempic Blindness: Weight Loss Drugs Linked to This Condition, Experts Warn - Tech Times - February 15th, 2025
- Ozempic Blindness Lawsuit Mounts: Shocking Side Effect Of Weight Loss Drug Is 'Eye Stroke,' What You Need To Know - IBTimes UK - February 15th, 2025
- The Politics Of Erasure: Gaza, Genocide, And The Wests Wilful Blindness OpEd - Eurasia Review - February 15th, 2025
- WHO launches new initiative to tackle the main cause of vision impairment - December 19th, 2024
- Blindness Advocates on Why There Should Be Audio Description Oscars - Variety - December 19th, 2024
- Diabetic retinopathy is treatable and preventable but only if you catch it in time - USA TODAY - December 19th, 2024
- AI: Could it help prevent blindness in diabetics? - BBC.com - December 19th, 2024
- Health Officials Investigate Rare Form of Blindness Tied to Ozempic - Gizmodo - December 19th, 2024
- Ozempic Could Be Blinding People Trying to Lose Weight - VICE - December 19th, 2024
- What is retinitis pigmentosathe vision disorder in the movie Blink? - National Geographic - December 19th, 2024
- VR shows promise in aiding navigation of people with blindness or low vision - Health Tech World - December 19th, 2024
- Ozempic could be linked to a common cause of sudden blindness, study finds - Quartz - December 19th, 2024
- New virtual realitytested system shows promise in aiding navigation of people with blindness or low vision - Tech Xplore - December 19th, 2024
- Ex-meth user who gouged her own eyeballs out while high says she is happier years after nightmarish episode - New York Post - December 19th, 2024
- Officials investigating link between Ozempic and eye-rotting disease that makes people blind - Daily Mail - December 19th, 2024
- Youngster to 'have eye removed' after minor fall - but NHS waitlist 'over 3 years' - NationalWorld - December 19th, 2024
- Restoring Vision: The Promise of Stem Cells in Healing Blindness - This is Local London - December 19th, 2024
- COAVS and Fred Hollows Foundation strengthen efforts to combat blindness in Pakistan - 24newshd - December 19th, 2024
- Study finds link between Ozempic and increased risk of vision loss - The Express Tribune - December 19th, 2024
- Going blind at 33 is devastating I wont see my childrens faces as they grow up - The Telegraph - December 19th, 2024
- Europol terror report reveals stark blindness about where the danger lies - Gript - December 19th, 2024
- Elton John lost his vision; signs and symptoms of eye infections that can cause blindness - The Times of India - December 6th, 2024
- Elton John's battle with blindness: How 77-year-old star's husband David Furnish guided him around premiere as - Daily Mail - December 6th, 2024
- Experimental study shows connection between COVID infection and age-related blindness - Medical Xpress - December 6th, 2024
- Elton John confirms shocking blindness after severe infection fight: I havent been able to see.. - Hindustan Times - December 6th, 2024
- Yes, an Eye Infection *Can* Lead To Vision Loss Heres How - Katie Couric Media - December 6th, 2024
- Elton John Battling Partial Blindness After Serious Eye Infection - Digital Music News - December 6th, 2024
- CU Anschutz researchers working to cure blindness through total eye transplantation - 9News.com KUSA - December 6th, 2024
- Elton John lost his vision from an eye infection. Here's why that might happenand how to prevent it - Fortune - December 6th, 2024
- Elton John announces blindness due to infection - CBS19.tv KYTX - December 6th, 2024
- David Frost: I suffer from face blindness. As a politician, being unable to identify people is agony - The Telegraph - December 6th, 2024
- Hes still standing how Elton John has survived far worse than blindness - The Telegraph - December 6th, 2024
- Foundation Fighting Blindness Partners with University of Colorado Anschutz Medical Campus and Other Leading Institutions to Secure Up to $46 Million... - December 6th, 2024
- Walmart helping low vison and blind customers shop with new app - KSLA - December 6th, 2024
- Elton John Says He Is Blind In The Right Eye Due to An Infection; What Is It All About? - Times Now - December 6th, 2024
- Trumps Win: The Blindness of Republicans and Democrats - The Times of Israel - December 6th, 2024