Some ocular help from man’s best friend

Novel gene-based therapy for achromatopsia demonstrates functional rescue of cone cells

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DENVER—Demonstrating the importance of investigating gene therapy and man’s best friend, researchers from Michigan State University (MSU) and the University of Pennsylvania have presented new preclinical data evaluating the efficacy of an investigational adeno-associated virus (AAV) vector gene therapy treatment developed by AGTC for achromatopsia (ACHM), a rare inherited retinal disease characterized by a partial or total absence of color vision. The study results were presented at the annual meeting of the Association for Research in Vision and Ophthalmology in May in Denver.
Entitled “Long-term Cone ERG Functional Rescue in CNGB3 Mutant Achromatopsia Dogs by AAV-hCNGB3 Vectors Containing the PR1.7 Promoter and Packaged in AAV5, AAV9 or Mutant AAV2 Capsids,” the abstract for the study describes the work to evaluate the efficacy of an experimental AAV vector expressing the human cyclic nucleotide gated channel beta 3 (hCNGB3) gene to restore function to cone cells (responsible for color vision) in the retinas of dogs affected by ACHM.
“These study results are promising and demonstrate that a novel, AAV-based gene therapy has significant clinical potential in treating achromatopsia,” according to Dr. András Komáromy, an associate professor in the MSU College of Veterinary Medicine and co-principal study investigator. “We are encouraged by the possibility of treating serious eye disease with gene therapy innovations. This is an important advancement, especially given the lack of available therapeutic options.”
“We are excited to contribute additional evidence suggesting that investigational gene therapies for treating inherited eye disorders show a high degree of potential,” echoes Dr. Gustavo Aguirre, a professor of medical genetics and ophthalmology in the University of Pennsylvania School of Veterinary Medicine and co-principal study investigator, noting that the data “highlight the effectiveness of the PR1.7 promoter in restoring cone cell function and support the further development of an AAV-PR1.7-hCNGBco vector for patients with achromatopsia.”
Aguirre notes that dogs are able to provide “an excellent large animal model of achromatopsia … which allows you to test therapies” for the disease, which can leave people able to only see in black, white and shades of gray.
Achromatopsia is also associated with stable central vision loss. The visual acuity of a person with complete achromatopsia is typically 20/200. In the incomplete form of achromatopsia the visual acuity may range from 20/60 to 20/100.
Aguirre tells DDNews that the research “clearly shows that treatment of cones to restore function is possible, and safe, and the pathway to a clinical trial is now evident.” The next step, he explains, is to conduct further vector development and preclinical safety studies, with the long-term goal “to take the data forward to a clinical trial” for a potential cure for achromatopsia.
Sue Washer, president and CEO of AGTC, tells DDNews that her company “has partnered with the Foundation Fighting Blindness on several projects to complete proof-of-concept work, toxicology and biodistribution studies needed to advance treatments for various retinal degenerative diseases to the clinic.”
AGTC’s “mission is closely related to blindness,” Washer says. “The company aims to use its proprietary gene therapy platform to develop products designed to transform the lives of patients with severe diseases in ophthalmology. Our lead product candidates focus on X-linked retinoschisis, achromatopsia and X-linked retinitis pigmentosa, which are inherited orphan diseases of the eye caused by mutations in single genes that significantly affect visual function and currently lack effective medical treatments.”
AGTC has an “overarching scientific rationale” for targeting these diseases, Washer notes, because “they are all well-characterized and there are highly predictive animal models available. Additionally, well‐defined endpoints that are commonly measured by clinicians simplify trial design and the regulatory process, and there is preliminary evidence for safe, targeted delivery in human trials.”
While there is currently no cure for ACHM, AGTC is developing a gene therapy product based on an AAV vector to enable expression of normal CNGB3 protein within cone photoreceptors and restore cone photoreceptor functions in patients. AGTC and its academic collaborators have previously demonstrated that subretinal delivery of gene sequences using an AAV vector restores cone responses in a dog model of ACHM.
“We are grateful to our academic research partners for their study support and guidance and look forward to continuing to advance our pipeline of AAV gene therapy products,” Washer has said in public comments. “We remain focused on our goal to provide treatments for serious eye diseases with significant unmet medical need.”

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