Research Update

Gene Therapy Shows Promising Results for Treating Inherited Retinal Disease

Achromatopsia is an inherited retinal disease (IRD) which is characterised by partial or complete colour blindness and affects approximately 1 in 30,000 individuals worldwide¹. People living with Achromatopsia have reduced visual acuity as a result of malfunctioning light-sensitive photoreceptor cells which capture the visual field, namely the cone photoreceptor cells which are located in the central region of the retina, called the macula. Cone cells are responsible for providing detailed central and colour vision.

Achromatopsia is caused by mutations (changes) in the DNA of these cone cells. DNA is the hereditary material of our body and is organised into genes, which, in normal circumstances, provide detailed instructions for making proteins to support growth and development. However, when the structure or amount of this DNA is altered in cone cells, this can have a detrimental impact on our sight and cause a decline in visual acuity.

Promising results from a clinical study indicate an improvement in visual function can be achieved and maintained over a 12 month period in people living with CNGA3-implicated Achromatopsia with a novel gene therapy². The CNGA3 gene is one of the most commonly implicated gene in Achromatopsia, involved in “25% to 28% of cases in Europe and the United States”, according to M. Dominik Fischer, MD, PhD and lead author of this study³.

In total, 9 individuals (8 men and 1 woman), all of whom had an advanced form of Achromatopsia, were recruited for this study. Overall, the subretinal gene therapy had an excellent safety profile with no serious adverse effects documented. Ameliorations in visual performance were recorded with respect to best corrected visual acuity and contrast sensitivity. On average, each participant’s best corrected visual acuity (BCVA) improved by 2.9 letters as per the Snellen eye chart from baseline to 1 year following treatment. Additionally, contrast sensitivity; the ability to detect the difference in brightness of separate objects and areas, improved by a mean of 0.33 log.

This study confirms proof of concept for subretinal gene therapy to treat Achromatopsia caused by a malfunctioning CNGA3 gene. Despite the need to confirm these results with a larger sample size and longer follow-up period, this study provides clear promise for a safe and effective treatment for Achromatopsia, for which none currently exists.

References:

1. National Institute of Health. Achromatopsia. Available at https://ghr.nlm.nih.gov/condition/achromatopsia. Accessed June 2020.
2. Fischer MD, Michalakis S, Wilhelm B, et al. Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial. JAMA Ophthalmol.2020;138(6):643–651. doi:10.1001/jamaophthalmol.2020.1032
3. Modern Retina. Subretinal gene therapy safe with visual benefit. Available at https://www.modernretina.com/view/subretinal-gene-therapy-safe-with-visual-benefit. Accessed June 2020.