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Chemical cousin of anti-anxiety drugs holds promise for psoriasis treatment


A new drug candidate previously shown to reduce harmful side effects of the autoimmune disease lupus also may be useful in treating psoriasis.

In a study published online Dec. 3 in the Journal of Pharmacology and Experimental Therapeutics, scientists from the University of Michigan report that a compound called benzodiazepine-423 (Bz-423)---a chemical cousin of the anti-anxiety drugs Valiumâ and Xanaxâ---suppresses cell growth in a model of psoriasis. In psoriasis, cells multiply unchecked, so inhibiting cell growth should help control the disease.

Psoriasis is a life-long genetic condition that affects the skin and joints. More than 4.5 million people in the United States have psoriasis or an associated form of arthritis, and the economic burden of the disease may be as high as $4.3 billion a year, according to the National Psoriasis Foundation.

"Currently, the best treatments for skin lesions associated with psoriasis are topical steroids, but the problem with those drugs is that they’re not selective for the disease-causing cells. They affect normal cells as well, and repeated use over time can lead to tissue destruction," said Gary Glick, who is the Werner E. Bachmann Collegiate Professor of Chemistry and a professor of biological chemistry in the U-M Medical School. "There are also protein drugs approved for use in treating psoriasis, but those drugs are injected instead of applied topically, which makes them more costly, less convenient and more likely to cause side effects since they are delivered throughout the body."

"What makes our compound particularly exciting is that it has the potential to be applied topically, and it shows very good selectivity for models of the disease-causing cells versus normal cells," Glick said. "So we believe the problems associated with repeated topical steroid use could possibly be alleviated with compounds like this."

Bz-423 has not yet been tested in people; the experiments described in the journal article were done on organ cultures of human skin designed to model psoriasis. However, said Glick, "with the data we have now and other data that we’re in the process of collecting, we hope to start a clinical trial in the near future."

The compound might also be added to Retin-A (retinoic acid), which is used to treat acne and skin damage due to sun exposure. "One of the problems with retinoic acid is that, while it’s very effective, it can also cause effects similar to psoriasis, so people often stop using it," Glick said. "Because the biological basis of retinoic acid hyperplasia (a reddening of the skin similar to inflammation) is very similar to that of psoriasis, the potential exists for our compound to be mixed with Retin-A to prevent these unwanted effects."

In 2003, Florida-based GMP Immunotherapeutics, Inc. (a subsidiary of GMP Companies, Inc.) entered into an exclusive patent license and a sponsored research agreement with the University of Michigan to develop Bz-423 and other compounds for treatment of lupus, rheumatoid arthritis, psoriasis and some forms of cancer. Glick and collaborators at U-M also are using the compounds to explore fundamental biological questions about the origins of such diseases.

Glick’s coauthors on the paper are James Varani, professor of pathology; Narasimharao Bhagavathula, a research investigator in the pathology department; Hilary Scherzer and Kevin Fay, research associates in pathology; Kent Johnson, professor of pathology; Sewon Kang, professor of dermatology; and Anthony Opipari, assistant professor of obstetrics and gynecology. Glick and Opipari are shareholders in GMP.

Nancy Ross-Flanigan | EurekAlert!
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