Achromatopsia (ACHM) is an inherited condition caused by mutations in one of several genes, the most common being the CNGB3 and CNGA3 genes. ACHM is associated with extremely poor visual acuity (most affected individuals are legally blind), extreme light sensitivity resulting in daytime blindness, and complete loss of color discrimination. There is no specific treatment for ACHM, although deep red tinted glasses or contact lenses can reduce symptoms of light sensitivity and daytime blindness.
AGTC is currently developing AAV gene therapy product candidates for the two most prevalent forms of ACHM. These forms of ACHM are caused by genetic mutations in the CNGB3 and CNGA3 genes, and together account for up to 75% of the ACHM patient population. In animal models of ACHM, untreated animals have the same signs of abnormal visual function as humans with ACHM, which is most dramatically manifested by daytime blindness under bright light conditions.
Treatment of ACHM animal models with an AAV vector expressing the CNGB3 or CNGA3 protein resulted in long-term improvement in visual function. In the video below, a dog affected by ACHM (caused by a CNGB3 mutation) is unable to navigate a maze. However, four months after being treated with a gene therapy product developed by AGTC, the dog is able to successfully navigate the maze. In the second video below, a sheep affected by ACHM (caused by a CNGA3 mutation) is first unable to navigate an obstacle course and is later shown navigating the same obstacle course successfully, three months after treatment with a gene therapy developed by AGTC.
Based on these preclinical proof-of-concept results, AGTC is currently conducting Phase 1/2 clinical trials to evaluate the safety and efficacy of the AAV gene therapy product candidates in patients with ACHM caused by CNGB3 or CNGA3 mutations.