GUCY2D Gene Therapy for LCA Shows Positive Results

Article: Gene Therapy Shows Promise in Initial Trial for Patients with Childhood Blindness
Source: Penn Medicine News, via Science Daily  and Technology Networks
Published: April 15, 2021

Structural differences in a normal retina
and in retinas with GUCY2D mutation

Researchers recently published initial results of a gene therapy for a form of Leber congenital amaurosis (LCA). Specifically, this gene therapy is the first-in-human clinical trial to target the GUCY2D gene in LCA, with initial results pertaining to three adult patients followed at nine months at this point. Normal copies of the GUCY2D gene encode an enzyme in the phototransduction pathway of the retina, allowing for light perception and vision. A lack of this enzyme prevents the recovery of this pathway, necessary for further signaling. Consequently, signals from the photoreceptors become very weak, manifesting as vision loss. However, despite weak signals and dysfunction, the photoreceptors often remain alive and structurally intact, spurring research into therapies via AAV viral vectors (injected subretinally in this case) to deliver functional copies of genes to those photoreceptors. The study reports that the first patient experienced substantial increase in rod sensitivity and improved pupillary response to light. The second patient experienced a smaller but sustained increase in rod sensitivity. And the third patient did not show improved rod sensitivity, although that patient did experience significantly improved visual acuity (a gain of 0.3 logMAR in the treated eye), which the researchers attribute to improved cone sensitivity and function. No toxicity effects were detected. These initial results demonstrate safety and efficacy for improved sensitivity of both rod and cone photoreceptors. The therapeutic dose used for these first three patients was the lowest dose the researchers intend to use in their study, and they hope to see continued safety and even greater efficacy at higher doses.

My rating of this study: ⭐⭐

Jacobson SG, Cideciyan AV, Ho AC, et al. "Safety and improved efficacy signals following gene therapy in childhood blindness caused by GUCY2D mutations." iScience. 10 April 2021. https://doi.org/10.1016/j.isci.2021.102409