In a treatment that restore sight to thousands of individuals with an inheritable condition called Leber’s Hereditary Optic Neuropathy (LHON), scientists are able to improve vision in both eyes in a majority of patients, even though just one eye was actually treated.
The treatment is an experimental sort of gene therapy, where tailored genetic material is injected to counteract genes that are defective or malfunctioning. With LHON, a m.11778G>A mutation in MT-ND4 gene is the target.
In phase 3 clinical test, 37 patients were treated with a modified viral vector rAAV2/2-ND4 in one eye only, resulting in a mean vision improvement of 15 letters on the standard ETDRS chart, you would possibly have spotted at an optician’s clinic.
“We expected vision to improve in the eyes treated with the gene therapy vector only,” said neuro-ophthalmologist, Patrick Yu-Wai-Man from the University of Cambridge.
“Rather unexpectedly, both eyes improved for 78% of the patients in the trial following the same trajectory over 2 years of follow-up.”
The eyes that did not get the gene therapy got a sham treatment instead and while the improvement wasn’t as great, it had been still substantial. Those in the earlier stages of LHON typically saw a much bigger improvement in their vision from treatment.
LHON is the commonest form of mitochondrial blindness transmitted from a mother to her children and attack the retinal ganglion cells damaging the optic nerves. Around 1 in 30000 people are thought to be affected, usually men in their 20s or 30s.
The replacement MT-ND4 gene treatment seems to rescue the retinal ganglion cells from their fate, causing results which will be “life-changing” consistent with the researchers. Normally less than 20% of these affected get their sight back.
“As someone who treats these young patients, I get very frustrated about the shortage of effective therapies,” says ophthalmologist José Alain Sahel from University of Pittsburgh.
“These patients rapidly lose vision in course of a few of weeks to a couple of months. Our study provides an enormous hope for treating blinding disease in young adults.”
While scientists know what causes the loss of vision, finding how to prevent it has proved difficult. LHON is a good candidate for gene therapy because it has a clear starting board & genetic targets that are relatively straightforward to hit.
What’s not clear yet is, why & how the gene therapy is spreading from one eye to the another. Follow-up experiments in macaque monkeys which have vision systems almost like humans suggested that the injected viral vector can spread to other tissue through some means of interocular diffusion but more research goes to be needed to know the mechanisms at work.
Gene therapy is now getting used to tackle a good range of diseases & health issues including those inherited from parents. Many other eye problems are in the sights of researchers and advances in one area can quickly help research in another, something that the team behind the present study is excited about.
“Our approach is not just limited to vision restoration,” says Sahel. “Other mitochondrial diseases might be treated using an equivalent technology.”
The research has been published in Science Translational Medicine.