n a landmark phase 3 clinical trial, the international team, coordinated by Dr Patrick Yu-Wai-Man from the University of Cambridge and Dr José-Alain Sahel from the University of Pittsburgh and Institut de la Vision, Paris, successfully treated 37 patients suffering from Leber hereditary optic neuropathy (LHON). Subject to further trials, the treatment could help thousands of people across the world to regain and retain some of their sight.
The study, published in the journal Science Translational Medicine, indicates that 78% of treated patients experienced significant visual improvement in both eyes. It suggests that the improvement in vision in untreated eyes could be due to the transfer of viral vector DNA from the injected eye.
LHON affects a specific type of retinal cells, known as retinal ganglion cells, causing optic nerve degeneration and rapidly worsening vision in both eyes. Within a few weeks of disease onset, the vision of most people affected deteriorates to levels at which they are considered legally blind. Visual recovery occurs in less than 20% of cases and few achieve vision better than 20/200 (largest letter on a standard eye chart). LHON affects approximately 1 in 30,000 people, mostly men, with symptoms usually emerging in their 20s and 30s. The majority of patients carry the m.11778G>A mutation in the MT-ND4 gene. Existing treatment for this blinding optic neuropathy remains limited.
“As someone who treats these young patients, I get very frustrated about the lack of effective therapies,” said senior investigator Dr Sahel, a professor of ophthalmology at the University of Pittsburgh. “These patients rapidly lose vision in the course of a few weeks to a couple of months. Our study provides a big hope for treating this blinding disease in young adults.”
The researchers injected rAAV2/2-ND4 – a viral vector containing modified cDNA – into the vitreous cavity at the back of one eye of 37 patients who had suffered vision loss for between 6 to 12 months. Their other eye received a sham injection. The technology, called mitochondrial targeting, was developed by the Institut de la Vision in Paris, France, and licensed to GenSight Biologics.
International coordinating investigator and neuro-ophthalmologist Dr Yu-Wai-Man, from Cambridge’s Department of Clinical Neurosciences and Moorfields Eye Hospital, London, said: “We expected vision to improve in the eyes treated with the gene therapy vector only. Rather unexpectedly, both eyes improved for 78% of patients in the trial following the same trajectory over two years of follow-up.”
Image: A young man's eye.
Credit: Phoenix Thomas via Pixabay
Reproduced courtesy of the University of Cambridge