Date: April 1st, 2004
A drug now in clinical trials for treatment of type 2 diabetes could eventually be used to promote longevity by treating or preventing major age-related diseases.
Scientists studying the drug fluasterone, a synthetic steroid, have so far shown that the drug lowers blood triglyceride levels, which are abnormally high in those with diabetes. They are now focusing on the fundamental question of whether it lowers blood glucose levels, and hope to have the drug on the market within a few years.
But Arthur Schwartz, a professor at Temple University and the lead scientist behind fluasterone, won't be finished with his drug if and when it makes it onto the market to treat diabetes. To him, this could be the medication that eventually extends our lives by treating such illnesses as cancer, heart disease, atherosclerosis, and Alzheimer's disease.
"It's not only moving along in theory, it's moving along in the clinical area. And to me, that's the key," he said. "I think we have a good crack at it."
To understand just why Schwartz is so optimistic, it helps to first understand the relationship that researchers have found between all these diseases.
The good and bad of inflammation
When the human body is exposed to infection, it fights back by flooding the infection site with white blood cells. These cells produce free radicals, which kill bacteria. Free radicals also cause inflammation and stimulate cell growth to help repair the site.
While these actions are necessary to ward off infection, they have their down side. Excessive inflammation and overzealous cell production have both been implicated as major contributing factors in the development of cancer, atherosclerosis, and Alzheimer's disease, as well as type 2 diabetes and insulin resistance.
Scientists have conducted a substantial amount of research to discover whether anti-inflammatory drugs would be effective treatments for these diseases. The results have been hopeful. Anti-inflammatory substances have repeatedly been shown to reduce incidences of tumor growth, heart disease, and diabetes in animals.
One such substance, a natural steroid known as DHEA, has long been proven effective against cancer and heart disease. DHEA works by inhibiting an enzyme known as G6PDH, which in turn lowers the production of another substance, NAPDH. NAPDH is necessary for the body to produce the free radicals that cause inflammation.
Knowing this, Schwartz wanted to answer the next big question: "How do we get a drug out of all this?" he asked. "Because DHEA has been around a long time, and no drug. All these exciting things in animals, but nothing in people. So I've been working very hard on this for years now."
The secrets of Sardinia
When Schwartz read studies about the small Italian island of Sardinia, he knew he was on to something. Genetically isolated, Sardinia is known for having a disproportionate number of male centenarians. Many of the men there share a common genetic trait: a deficiency of the G6PDH enzyme.
Aging researchers have clamored for data on the Sardinian population to find out what secrets these men hold in their genes. Studies have confirmed that the G6PDH-deficient men are far less likely than the general population to die from heart disease or stroke and are far more likely to live to 100. This provides strong human support for the opinions held by Dr. Schwartz and others that a drug that inhibited the production of G6PDH, and all the processes that come with it, would be a step in the right direction for treating many age-related diseases.
"It's very suggestive," Schwartz said. "And from what we know about inhibiting G6PDH in animals, it's more than suggestive. It suggests that it's probably real."
So where's the drug?
The problem is that anti-inflammatory drugs are not without their own issues. Often, they must be used in extremely high dosages, which cause unacceptable side effects in people. Aspirin, for example, reduces inflammation in very high doses and has actually been shown effective for treating diabetes. But high doses of aspirin also cause ringing in the ears, bleeding in the stomach, and ulcers.
DHEA, too, can be unhealthy despite its benefits. Taken at the high doses necessary to get results, DHEA elevates testosterone levels. This in turn lowers good blood cholesterol and worsens insulin sensitivity. So Dr. Schwartz's team modified the steroid to eliminate this effect while maintaining its anti-inflammatory properties - and came up with fluasterone.
"Fluasterone is just a steroid that, for a variety of reasons, does not go to testosterone, but still works," he said.
Once the fluasterone researchers have completed the trials that are underway, they will know better what dosage the drug requires to be effective, and how best to administer it. If it is proven effective and goes to the market to treat type 2 diabetes, the next step will then be to test it for effectiveness against other diseases. And the longevity drug Schwartz has envisioned for years may become a reality.