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Little-known drug may halt multiple sclerosis, Gladstone study finds

Gladstone senior investigator Dr. Eric Verdin: "It is a very complex but significant target."

Blocking a specific protein with a little-known, experimental drug restored balance in the immune systems of lab mice, preventing them from developing multiple sclerosis, researchers at San Francisco's Gladstone Institutes found.

The early research, published Monday in the Journal of Experimental Medicine, could chart a new course for the drug against MS, a potentially fatal disease where the immune system runs amok and attacks nerve cells' protective covers.

But the researchers note that some scientists — including one now at Google Inc.-backed Calico Life Sciences LLC — have thought that enhancing the same protein could slow the aging process.

Much research remains to be done, said Dr. Eric Verdin, co-senior author of the study and a senior investigator at the University of California, San Francisco-affiliated Gladstone Institutes. "I don't want to raise false hopes," he said.

Still, it is the balance between the potential anti-aging promise of activating the protein — called sirtuin 1, or SIRT1 — and its harmful role in inflammation in MS patients that makes it intriguing, Verdin said.
The findings also underscore the delicate seesaw action of the immune system in protecting us from disease without going hyperactive and attacking our bodies instead.

Gladstone researchers found that an experimental drug called EX-527, which was developed by shuttered Elixir Pharmaceuticals Inc., inhibited production of SIRT1 in laboratory mice engineered to develop MS. That blocking action protected the mice against the onset of MS, researchers said.

Whether the drug could work in humans is unknown, Verdin said. Several drugs have shown promise in mice, only to fail in humans. But, he added, EX-527 or other SIRT1 inhibitors potentially could halt diseases — such as MS or type 1 diabetes — where inflammation or autoimmunity play a destructive role.

The "true value" of a SIRT1 inhibitor could come in a disease such as type 1 diabetes, previously known as juvenile diabetes, Verdin said. About 1.25 million Americans have type 1 diabetes, according to the American Diabetes Association, but that number is growing. In comparison, some 400,000 people in the United States have multiple sclerosis, according to the Multiple Sclerosis Foundation.

Help or hurt?
SIRT1 is involved in the production of so-called "T-helper cells," a type of white blood cell that serves as the immune system's scout against foreign invaders, such as viruses and bacteria. At the same time, the protein has a negative impact on the maturation of regulatory T cells that typically help maintain the immune system's balance and that put the brakes on autoimmunity, the hyperactivity of the immune system.

So, a SIRT1 inhibitor could simultaneously blunt the production of T-helper cells that turn destructive in MS patients and boost production of regulatory T cells that provide balance.

That give-and-take is only part of the intrigue surrounding SIRT1 and EX-527.
The drug was developed by Elixir Pharmaceuticals of Cambridge, Mass., and subsequently licensed by Italy's Siena Biotech S.p.A. Siena in late 2009 started an early clinical trial of EX-527 focused on Huntington's disease.

Story Source: The above story is based on materials provided by SANFRANCISCOBUSINESSTIMES
Note: Materials may be edited for content and length

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