The Promise of Gene Therapy for Diabetes

Article excerpt

Can gene therapy ease the pain of diabetic neuropathy?

The pioneering work of renowned gene therapist Dr. Jeffrey Isner of St. Elizabeth's Medical Center of Boston resumes, as colleagues launch a new trial using a novel gene therapy to alleviate the suffering of patients with diabetic neuropathy. According to the Neuropathy Association, some 20 million Americans suffer from various forms of neuropathy, a potentially serious condition caused in part by blockage of small blood vessels within the nerves in the legs, with diabetes as the most common cause.

St. Elizabeth's is now enrolling patients in an NIH-funded trial to evaluate the safety and impact of VEGF (vascular endothelial growth factor) gene transfer in these patients. Post readers will remember the tremendous success and improvement in the quality of life among patients enrolled in the coronary gene therapy trials, led by Dr. Jeff Isner (Mar./Apr. and May/June 2000 SEP).

While conventional medications can ease the symptoms of the condition, diabetic neuropathy has to date been considered irreversible. However, data gleaned from an early clinical trial, conducted by Dr. Isner and his team, suggested that diabetic neuropathy may be improved with gene therapy. Last year, a preliminary study conducted at Caritas St. Elizabeth's, published in Archives of Neurology, indicated that a related problem called ischemic neuropathy could be reversed using the gene transfer of VEGF.

To learn more about the promising new research and ongoing trial, the Post spoke with Allan Ropper, M.D., chief of neurology at Caritas St. Elizabeth's Medical Center of Boston.

Post: Could you tell readers about this new NIH-funded gene transfer trial for diabetic neuropathy?

Ropper: About half of all people with diabetes will develop some degree of nerve damage-mainly in their legs-as a result of longstanding diabetes. Ten percent of patients have these symptoms when diabetes-both type 1 and type 2 (adult onset)-is first discovered. For some people, the problem is quite severe, with symptoms that include numbness, pain, and foot and leg weakness. In other individuals, the condition might include problems relating to the bowel, bladder, and so forth. The symptoms are a manifestation of damage to peripheral nerves, and as such, the problem is generally referred to as peripheral neuropathy.

In the United States, diabetes is the most common cause of peripheral neuropathy. At the moment, there is no specific treatment for the nerve problem. It has been recognized that very rigid control of the blood sugar can reduce the progression of the nerve damage, but it certainly does not improve the condition. And the degree of control required to stabilize the problem is very difficult to attain. Neurologists, general physicians, and endocrinologists who see these patients have to resort to treating the symptoms with a variety of medications.

Post: Is this the first trial to examine the role of gene therapy in treating diabetic neuropathy in the United States?

Ropper: Yes, this is the first trial of gene therapy in peripheral nerve disease that we are aware of. We recently enrolled our first patient. There is a fairly elaborate prescreening process, so the patient hasn't received the gene yet, but this is the initiation of the trial.

Post: What conventional medications are presently used to treat the condition?

Ropper: At the moment, physicians prescribe medications used in the treatment of epilepsy, such as gabapentin (Neurontin), and potent pain medicines, among others. These medications, however, simply reduce the symptoms of the disease and do not address the fundamental problem in the nerves.

Post: How did you become involved in the application of gene therapy to treat diabetic neuropathy?

Ropper: The story began in the mid-'90s when Dr. Jeff Isner was investigating the use of vascular endo-thelial growth factor (VEGF) for blocked large arteries. …