Easing The Pain of Diabetes
pilotonline.com
Dec. 28, 1998
EVMS researchers are testing new drugs that may help diabetes patients who suffer nerve-cell damage.
The article mentions Regeneron and Amgen's work on NT3; Genentech's Nerve Growth Factor, and Vertex's Timcodar.
EVMS=Eastern Virginia Medical School)
Several of the NT3 clinical trials are being carried out at The Research Institute of the LEONARD R. STRELITZ DIABETES INSTITUTE.
evms.edu
Some excerpts:
<Until recently, diabetic neuropathy was considered irreversible. Damaged peripheral nerve cells either don't grow back, or grow so slowly that they can't compensate for the damage of diabetes.
Lately, however, doctors have been looking at ways to make the body do what it does in the embryo stage -- grow lots and lots of nerves.
Why diabetes kills nerve cells isn't completely understood. One possibility is that glucose, or blood sugar, attaches itself to the membranes covering nerve cells. The body's immune system no longer recognizes these cells and attacks them, destroying the membranes. Because the membranes help speed along messages passing through nerve cells, the nerves don't work as well.
While Genentech's drug re-grows small peripheral nerve fibers, it doesn't seem to help large fibers, which are responsible for the body's ability to move muscles and maintain balance and coordination.
Diabetics, for example, are much more likely to suffer serious falls and fractures than people without the disease.
''No matter how hard you make your bone, if you stagger and you fall, you break,'' Vinik said.
Patients may lose the ability to do simple things, like button a shirt. As their skills deteriorate, they often drop out of society, tired of struggling or fearful of embarrassing themselves.
''They become very apathetic,'' Vinik said. ''They become very withdrawn, depressed.''
To sprout more large nerve fibers, EVMS doctors have been testing a substance called NT3.
It's made by Amgen, a California drug company, and a smaller company called Regeneron.
Norfolk, which had 29 patients in the experiment, was the largest of six centers nationally that took part in the trial.
After treatment with NT3, Vinik said, his patients saw their reflexes improve, regained their balance and found they were better able to grip things.
''They felt a lot better about themselves, so they went out, they socialized,'' he said.
The biggest drawback to NT3, and Genentech's Nerve Growth Factor, is the method of treatment -- patients must give themselves injections. Though diabetes patients may be used to insulin injections, the process is still unpleasant and inconvenient.
The problems of delivering the drug have led companies to look for different ways of fixing damaged nerves. Could doctors spur the body to do the repair work itself?
So they are looking at using a type of small molecule engineered for the task. Taken in a pill, the molecules would work by a complicated process to spur the body to create a chemical substance that causes nerves to grow.
''Small'' is a key concept here. A single molecule of insulin, for example, weighs about 6,000 kilodaltons; one of these engineered molecules would weigh just 100 to 200 kilodaltons, small enough to be ignored by the body's immune system, which destroys foreign invaders.
''They can slip around unnoticed,'' Vinik said.
The molecular treatment, called Timcodar, was developed by Vertex, a Charlottesville company. The drug did well in animal studies; EVMS and several other centers have just started trials in humans to determine whether it is safe and effective. >
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