LCA Gene Therapy Restores Vision in Canines

Article: Turning back the clock on a severe vision disorder
Source: University of Pennsylvania, via ScienceDaily  and NEI
Published: March 30, 2021

Photoreceptor regrowth (red) in the retinas
of canines with NPHP5-related LCA

Veterinary ophthalmologists and vision scientists studying a severe form of the rare eye disease Leber congenital amaurosis (LCA) have developed a gene therapy that restored vision in a canine model of the disease. Specifically, the variant of LCA they studied is caused by a mutation in the NPHP5 gene, resulting in abnormal or incomplete development of the cilia of photoreceptors. Among the spectrum of LCA vision disorders, the one caused by the HPHP5 gene is one of the rarest, affecting about 5,000 people worldwide. It is also one of the most severe and children with this form of LCA are not visual. In people with NPHP5 LCA, the rod photoreceptors degenerate early in the disease and the cones survive, albeit abnormally structured and without function. The fact that the cone photoreceptors persist in this form of LCA led the researchers to consider a gene therapy that would not only prevent early degeneration of photoreceptors but possibly even reverse vision loss. Investigating this hypothesis in dogs with a nearly identical naturally occurring form of the disease showed incredible promise. The researchers used gene augmentation therapy, in this case delivering a normal copy of either the canine or the human version of the NPHP5 gene via intravitreal injection in one eye of nine five-week-old dogs with the vision disorder. They then used electroretinography (ERG) and optical coherence tomography (OCT) to determine the effectiveness of the treatment. OCT imaging showed that the outer segments of the cones in treated eyes regrew. Even more encouraging were the functional visual outcomes. At six months, the dogs' vision was tested using an obstacle-avoidance course. When the dogs' treated eye was blindfolded, they had difficulty navigating, but when that eye was not covered, the ability to avoid obstacles was notably improved. As the researchers are keen to point out, these results show not only halting disease progress but also restoring visual function. Although affecting only a small number of people, the fact that a large animal model of NPHP5 disease very closely parallels the disease in humans lends support for clinical trials to investigate the potential benefit in children with this form of LCA.

My rating of this study: ⭐⭐🌸

Aguirre GD, Cideciyan AV, Dufour VL, et al. "Gene therapy reforms photoreceptor structure and restores vision in NPHP5-associated Leber congenital amaurosis." Molecular Therapy. 27 March 2021. https://doi.org/10.1016/j.ymthe.2021.03.021