Restoring eyesight through gene therapy

Only a few patients have been tested so far, but the prospect of restoring sight to patients with a specific genetic condition is being tested. You can see the Good Morning America presentation and read news articles about the procedure here.

The inherited retinal disease is called leber congenital amaurosis; it prevents the retina from processing light.

The treatment is very quick--surgery lasting only an hour--but the preparation for the ability to transfer the key gene into the retina has taken over 10 years. It was especially interesting to me to hear that the profiled patient came to the States for her treatment because she couldn't find treatment where she lived. According to an excellent and informative site that gives information on gene therapy:

• A team of British doctors from Moorfields Eye Hospital and University College in London conduct first human gene therapy trials to treat Leber's congenital amaurosis, a type of inherited childhood blindness caused by a single abnormal gene. The procedure has already been successful at restoring vision for dogs. This is the first trial to use gene therapy in an operation to treat blindness in humans. See Doctors Test Gene Therapy to Treat Blindness at www.reuters.com (May 1, 2007).

Because the site has not been updated since mid-2007, these "successes" should be reconsidered in light of today's announcement. I will try to find out what I can about the people who had treatment in the UK almost a year ago.

Meanwhile, the following information may be helpful in understanding the factors that have kept gene therapy from becoming an effective treatment for genetic disease:

• Short-lived nature of gene therapy - Before gene therapy can become a permanent cure for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Problems with integrating therapeutic DNA into the genome and the rapidly dividing nature of many cells prevent gene therapy from achieving any long-term benefits. Patients will have to undergo multiple rounds of gene therapy.

• Immune response - Anytime a foreign object is introduced into human tissues, the immune system is designed to attack the invader. The risk of stimulating the immune system in a way that reduces gene therapy effectiveness is always a potential risk. Furthermore, the immune system's enhanced response to invaders it has seen before makes it difficult for gene therapy to be repeated in patients.
• Problems with viral vectors - Viruses, while the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient --toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause disease.
• Multigene disorders - Conditions or disorders that arise from mutations in a single gene are the best candidates for gene therapy. Unfortunately, some the most commonly occurring disorders, such as heart disease, high blood pressure, Alzheimer's disease, arthritis, and diabetes, are caused by the combined effects of variations in many genes. Multigene or multifactorial disorders such as these would be especially difficult to treat effectively using gene therapy.

The site also includes a wealth of other background information.

Marie Godfrey, PhD