Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis

A form of Leber's congenital amaurosis is caused by mutant RPE65 , a critical component of the visual cycle. Two early clinical trials to assess subretinal injection of a viral vector containing RPE65 in young adults with advanced retinal degeneration show that this approach is generally safe in the short term, although one group reported an adverse event: macular hole. The authors observed improvement in some measures of visual function. Two early clinical trials to assess subretinal injection of a viral vector containing RPE65 in young adults with advanced retinal degeneration show that this approach is generally safe in the short term, although one group reported an adverse event: macular hole. The authors observed improvement in some measures of visual function. Leber's congenital amaurosis is a term used to describe a group of recessively inherited, severe, infantile-onset rod–cone dystrophies. 1 Mutation of one of several genes, including RPE65 , causes disease that involves impaired vision from birth 2 , 3 and typically progresses to blindness in the third decade of life. There is no effective treatment. RPE65 is expressed in the retinal pigment epithelium and encodes a 65-kD protein that is a key component of the visual cycle, 1 , 4 – 8 a biochemical pathway that regenerates the visual pigment after exposure to light. 9 – 14 A lack of functional RPE65 results in deficiency of 11- cis . . .