Putting a stop to nerve damage
One of the more serious complications of diabetes is a disabling condition called diabetic neuropathy. Because people with diabetes have excessive levels of blood sugar, nerves can become damaged, causing sharp pain that disturbs sleep, numbness in the hands or feet, digestive problems, ulcerations that can lead to foot amputations, and even sudden death if the nerves to the heart are affected.
Now an experimental drug, which attacks the underlying cause of the nerve injury, may be able to halt or reverse this damage. Diabetic neuropathy is “insidious because it’s difficult to diagnose and people often don’t realize they are even symptomatic until there is major damage,” says Dr. Francine R. Kaufman, a diabetes expert at USC’s Keck School of Medicine and author of “Diabesity.” “Potentially this could be a great breakthrough.”
About half of the people with diabetes -- or about 3.5 million Americans -- will, over time, develop some form of neuropathy. Even meticulous control of blood sugar won’t completely protect against the condition. Scientists still don’t understand the exact mechanism of damage, but they say it’s linked to the high glucose levels that allow two forms of sugar, sorbitol and fructose, to collect in the nerves.
Prolonged exposure to these sugars damages the nerves that control muscle movement and the sense of touch, and interferes with their ability to transmit signals from the brain. Symptoms may include burning, shooting or stabbing pain; nausea and indigestion; and numbness in the hands and feet. This numbness can be especially dangerous because people don’t realize they’ve hurt themselves and the untreated sores can become infected.
“When the nerve damage becomes more advanced, you can step on a nail or thumbtack and not be aware you are injured,” says Dr. Thomas Brannagan III, a neurologist at Cornell University’s Weill Medical College in New York. And because the impaired nerves interfere with blood circulation, wounds don’t heal properly, causing severe ulcerations. Each year, about 85,000 diabetic Americans have a limb amputated because of these injuries.
The new drug, called Ranirestat, may reduce or even reverse the debilitating nerve damage. The pill works by halting the action of an enzyme, aldose reductase, that normally converts the excessive glucose found in diabetics into sorbitol and fructose. “If you stop what is attacking the nerves, they have the ability to regenerate,” says Brannagan, who is testing the new drug.
A 2004 study that involved 101 patients was encouraging. Two-thirds of the volunteers received either five or 20 milligrams of the drug once a day; the remainder got a dummy pill. After 12 weeks of treatment, sorbitol concentrations in the nerves fell by up to 83.5% in participants who received the highest dosage of the drug, compared with the placebo group. Fructose levels were similarly inhibited, and transmission of nerve signals was improved.
“This was an amazing reversal of abnormal activity because it’s unusual to see this much change in such a short period,” says Dr. Vera Bril, a neurologist at the University of Toronto who conducted this study. When treatment was extended for an additional 48 weeks, these results were maintained and, in some cases, patients experienced even greater improvements, though the actual numbers have yet to be released.
A larger test was recently launched by Japan’s Dainippon Pharmaceuticals, the maker of Ranirestat. It will eventually encompass 480 volunteers, who will be testing even larger doses of medication, at about 20 sites in North America. “So many therapies haven’t worked in the past, but this seems like a really potent drug,” says Bril. “For the first time, I’m really hopeful.”
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An alternative
Another experimental drug, Ruboxistaurin, has also shown promise in counteracting diabetic neuropathy. Although it is expected to be on the market earlier than Ranirestat -- possibly as soon as next year -- evidence suggests it is not as potent.
The medication blocks the action of PKC (protein kinase C) beta, an enzyme that becomes overactive in diabetics and that damages small blood vessels. A yearlong study involving 205 patients revealed that volunteers on the test medication, which increases blood flow, achieved significant improvement in measures of their symptoms of neuropathy.
