- Leber hereditary optic neuropathy (LHON) affects 1 in 50,000 people.
- A team of scientists conducted a clinical trial to test gene therapy as a potential treatment for vision loss from LHON.
- Results of the phase 3 trial results revealed improved vision in both eyes for 78% of the patients.
In 2016, an international team of scientists began the REVERSE trial with an aim to assess the effectiveness of gene therapy in correcting vision loss due to LHON. They recruited 37 LHON patients carrying the mtDNA (mitochondrial DNA) mutation. Moreover, the patients had been suffering from impaired vision for a duration of 6 to 12 months.
As part of the phase 3 trial, each participant received a single intravitreal injection of rAAV2/2-ND4, a gene therapy vector. And, a sham injection, or a placebo, in the other eye. Researchers tested the participants’ vision 48 and 96 weeks post-treatment. They published their findings in the journal Science Translational Medicine.
Gene Therapy Improves Vision for 78% of Patients
Mutations in the MT-ND4 gene is the most common cause of LHON. Therefore, researchers developed a viral vector against this particular gene. According to Dr. Yu-Wai-Man, the gene vector works by replacing the defective MT-ND4 gene. Thus, rescuing the retinal ganglion cells from degenerating.
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 2 years of follow-up.
Dr. Yu-Wai-Man, International coordinating investigator
On average, the vision in the treated eye improved by 15 letters. Whereas, in the sham eye it improved by 13 letters. An unexpected and significant improvement. Furthermore, results showed that the eye treated with the gene vector was three times more likely to achieve a vision of 20/200 or better.
Researchers believe that gene therapy can likely treat blindness in people across the world. And possibly help treat further mitochondrial diseases.
Leber hereditary optic neuropathy
Although extremely rare, Leber hereditary optic neuropathy (LHON) is the most common cause of mitochondrial blindness. The bilateral vision loss occurs as a result of degeneration of the retinal ganglion cells. Symptoms generally begin as a unilateral loss of central vision that can progress into bilateral vison loss within weeks to months. The disease mostly affects young male adults in their 20s and 30s.
As someone who treats these young patients, I get very frustrated about the lack of effective therapies. 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.
Dr. José-Alain Sahel, principal investigator
The current treatment options for LHON involve rehabilitation services and with the use of visual aids. However, only 20% of patients recover their vision. Moreover, an improvement in vision greater than 20/200 is extremely rare.
The team, later on, conducted a study in cynomolgus macaques to investigate how the bilateral vision improvement came into being. According to the results, the gene vector likely moved into the sham eye through interocular diffusion. However, further studies are required to confirm the findings.
Reference:
Yu-Wai-Man, Patrick, et al. “Bilateral Visual Improvement with Unilateral Gene Therapy Injection for Leber Hereditary Optic Neuropathy.” Science Translational Medicine, vol. 12, no. 573, 2020, doi:10.1126/scitranslmed.aaz7423.
