This article is more than 5 years old. Information may no longer be current.
Gene therapy may be an option for restoring vision in congenital blindness
Some low-light sensitivity was restored in a trial of three patients with Leber’s congenital amaurosis.
Click Here to Manage Email Alerts
Gene replacement therapy restored some visual sensitivity in low-light conditions in a trial of three patients with Leber’s congenital amaurosis type 2, and there were no significant immune responses to the carrier virus used to transport genetic material to the retina, according to a study.
 Paul A. Sieving |
The preliminary results are an important proof of principle of the viability of gene therapy for at least some ocular genetic diseases, according to Paul A. Sieving, MD, PhD, director of the National Eye Institute at the National Institutes of Health. The study, published in Human Gene Therapy, was sponsored by the National Eye Institute. Two other studies that were funded by other sources were published earlier this year and also showed successful retinal gene replacement therapy.
Leber’s congenital amaurosis type 2 is caused by mutations in the RPE65 gene, which is essential for production of rhodopsin, the light-sensitive molecule within the retina.
Same conclusion
“These three groups worked independently on the same system, meaning vision, photoreceptors, and pigment epithelium and this particular gene, and all three experiments came to the same conclusion: that restoring a functional RPE65 gene can partially repair the fundamental vision defect in this condition of childhood blindness,” Dr. Sieving told Ocular Surgery News in a telephone interview.
For this study, William W. Hauswirth, PhD, at the University of Florida’s Powell Gene Therapy Center, and Samuel Jacobson, MD, PhD, at the Scheie Eye Institute of the University of Pennsylvania, introduced the RPE65 gene, which codes for an enzyme that allows photoreceptor visual pigments to absorb photons and maintain sight. They used an adenovirus-associated virus vector administered through a subretinal injection.
According to the study, no vector-associated complications were noted in the three patients, and neither significant humoral nor cellular immune responses were noted. In addition, “all three patients noted increased light sensitivity in the study eye but to different degrees. These observations were most evident to the patients under low ambient light conditions and when using their control eye as comparators,” the study said.
‘Tremendous applicability’
Future research, Dr. Sieving said, will look at this and other vectors to introduce other genes as therapy to the eye, as well as a way to regulate gene expression through controllable promoters.
“This is a demonstration in a nearly designer disease, one in which restoring enzyme action resulted in a change in state in which vision goes from inability to respond to light to an ability to respond to light. It is remarkable, but this was proof of principle, and that is the way I would take it at this moment,” Dr. Sieving said. “It has tremendous applicability both in vision and across human diseases more generally.” – by Bryan Bechtel
Reference:
- Hauswirth WW, Aleman TS, Kaushal S, et al. Phase I trial of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results. Hum Gene Ther. 2008 Sept 7. [Epub ahead of print]
- Paul A. Sieving, MD, PhD, can be reached at National Eye Institute, 31 Center Drive, Building 31, Room 6A03, Bethesda, MD 20892-2510; 301-496-2234; fax: 301-496-9970; e-mail: pas@nei.nih.gov.
