Scientists discover new drug candidates for cystic fibrosis and other diseases

November 01, 2011

Bethesda, MD--A new discovery by Californian scientists may lead to a pharmaceutical breakthrough for a wide range of illnesses that involve the hydration of cells that line the inner surfaces of our body's organs and tissues. In a new report appearing in the FASEB Journal (http://www.fasebj.org), the researchers describe how they used high-throughput screening to identify small-molecule drug candidates which help cells bypass defective channels that normally move salt and water through cell membranes. These drug candidates work by activating an alternative chloride channel called "TMEM16A" that might be effective in treating conditions such as cystic fibrosis, dry eye and dry mouth diseases and slow-transit constipation.

"Further pre-clinical development of the chloride channel activators identified in our study may lead to new drug therapies for cystic fibrosis, dry eye and mouth syndromes, and certain types of constipation," said Alan S. Verkman, M.D., Ph.D., study author from the Department of Medicine at the University of California, San Francisco.

Verkman and colleagues discovered these compounds by using high-throughput screening, in which more than 100,000 drug-like compounds were tested for their ability to activate the TMEM16A channel. Active compounds coming from the screen were further improved and tested in cell and mouse models. These compounds were found to help facilitate salt and water movement, making them promising drug candidates.

"Scientists have known for decades that cells have more than one way to move salt and water. Indeed, over the years many useful drugs have been developed that influence these movements in the heart and kidneys," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "This discovery is important not only because it identifies a new channel present all over the body, but finds a promising agent to activate it. As further drug candidates are devised to target TMEM16A, this work may lead to clinical advances of major significance."
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Receive monthly highlights from the FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal (http://www.fasebj.org) is published by the Federation of the American Societies for Experimental Biology (FASEB) and celebrates its 25th anniversary in 2011. Over the past quarter century, the journal has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century and is the most cited biology journal worldwide according to the Institute for Scientific Information.

FASEB comprises 24 societies with more than 100,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB enhances the ability of scientists and engineers to improve--through their research--the health, well-being and productivity of all people. FASEB's mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

Details: Wan Namkung, Zhen Yao, Walter E. Finkbeiner, and A. S. Verkman. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction. FASEB J. November 2011 25:4048-4062; doi:10.1096/fj.11-191627 ; http://www.fasebj.org/content/25/11/4048.abstract

Federation of American Societies for Experimental Biology

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