New approach for attacking lupus ...( NEW YORK CITY Dec. 16 2007 Investiga...)

NEW YORK CITY, Dec. 16, 2007 Investigators at Hospital for Special Surgery have identified two new targets for drugs aimed at controlling lupus. If companies are able to develop drugs that hone in on these targets, patients may be able to control their disease with few side effects.

The study identifies very good therapeutic targets, and what needs to be done is identify better candidate drugs, said Lionel Ivashkiv, M.D., director of Basic Research at Hospital for Special Surgery in New York City. He led the study, which was published online in Nature Immunology on December 16 and will appear in print in February.

Because abnormally high levels of interferon-alpha can lead to lupus, researchers have developed drugs that block interferon. These drugs, however, have immunosuppressive side effects that can leave patients vulnerable to various illnesses and infections, some of which can be deadly. Currently, these drugs are being tested in clinical trials. If researchers are able to develop drugs for the newly identified drug targets, patients may be able to avoid these immunosuppressive effects.

Interferons have two major functions. First, they protect against viruses and second, they regulate immune responses, strengthening immune responses and playing a role in autoimmunity. Different proteins, called STATs, mediate the two functions of IFN. STAT1 mediates the autoimmune and inflammatory functions, and STAT2 mediates the virus protection function. What we were interested in understanding is how you can regulate the balance between activating the inflammatory effects and the antiviral effects, Dr. Ivashkiv said. We thought if we could control the functions of the interferons, that would lead to new therapeutic approaches where you could block specifically some of their functions, but not others.

The investigators discovered that calcium specifically increases activation of STAT1 by interferons, and thus turned their attention
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