april 2008
LCA Gene Therapy Results
Trials to test the safety of gene therapy on LCA patients with the RPE65 mutation have been ongoing in both the U.S. and the U.K. Both teams released reports on these studies in the New England Journal of Medicine on April 27, 2008 and the results are promising!
The Therapy
There are ten known gene mutations that cause LCA, one of which is a mutation in the RPE65 gene (also called LCA2 which is thought to cause about 6% of all known LCA cases). This defect also occurs naturally in dogs and, after years of research, doctors have developed a gene therapy technique that, while not necessarily curing the dogs of their blindness, does stop the disease in its tracks and improve vision at the same time.
These doctors have created a virus (they call it a vector) that carries the protein that the RPE65 gene lacks. The virus is then injected directly into the retina. In order to inject the virus into the patient's eye, the doctors must first detach a small portion of the retina. Once injected, the virus sort of fills in the gaps and repairs the defective gene, and then, if all goes well, the gene will function normally and the retina will stop degenerating—and maybe even begins to heal a bit. This is a very simplified version of the process, of course, but that's the basic concept behind the therapy.
The Patients
Phase I trials to test this gene therapy have been underway in both the U.S. and the U.K. Phase I trials are more concerned with safety than efficacy so the patients were injected with small doses of the virus and monitored closely for any adverse effects.
Both studies tested three patients each (six patients in all) between the ages of seventeen and twenty-six. The patients needed to be young because the doctors wanted to find patients with retinas that weren't yet too damaged. In the next phase of the study the doctors hope to test the therapy on even younger patients.
The Results
The best news to come from these trials is that there does not seem to be any adverse effects from the therapy. This means that the gene therapy is safe and that the trials can continue into Phase II where they will test larger doses on younger patients.
Surprisingly, the doctors also reported some improvement in vision as well! This wasn't really expected at this point since they weren't using a full dose of virus. In the U.K. one of the three patients saw improved night vision while in the U.S. all three patients showed "modest improvement in measures of retinal function on subjective tests of visual acuity." This is very exciting and bodes well for future studies.
Resources
We sorted through many articles online and in newspapers to find the most relevant information on the trials to post here. If you want to read more, here are a few of the better articles:
- UCL Institute of Ophthalmology:
Results of World's First Gene Therapy for Inherited Blindness Show Sight Improvement - The Philadelphia Inquirer:
Philadelphia Researchers Bring Sight to the Blind - The New England Journal of Medicine:
Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis (U.K. study)
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis (U.S. study)
You may also want to read about the genetics behind LCA at The Foundation for Retinal Research.
Donations
Are you interested in supporting this research? You can make donations to
The Foundation for Retinal Research or The Children's Hospital of Philadelphia.