Amyloid blockers may be a dead end

With few approved drugs available to treat Alzheimer disease, researchers are working on new compounds that block amyloid formation. But many potential drugs in the pipeline for the disease and other amyloid-associated illnesses may not be as promising as thought, according to a new linkurl:study;http://www.nature.com/nchembio/journal/vaop/ncurrent/abs/nchembio.65.html published today (January 27) in Nature Chemical Biology. The research, led by linkurl:Brian Shoichet;http://ucsf.edu/dbps/facu

Andrea Gawrylewski
Jan 26, 2008
With few approved drugs available to treat Alzheimer disease, researchers are working on new compounds that block amyloid formation. But many potential drugs in the pipeline for the disease and other amyloid-associated illnesses may not be as promising as thought, according to a new linkurl:study;http://www.nature.com/nchembio/journal/vaop/ncurrent/abs/nchembio.65.html published today (January 27) in Nature Chemical Biology. The research, led by linkurl:Brian Shoichet;http://ucsf.edu/dbps/faculty/pages/shoichet.html at the University of California, San Francisco, examined the action of eight compounds that are known to inhibit protein aggregation and linkurl:amyloid formation; -- some of which are in early stage testing as therapies. Using electron microscopy, the group demonstrated that the compounds do block linkurl:amyloid formation;http://www.the-scientist.com/2007/11/1/78/2/, but inhibit linkurl:other proteins;http://www.the-scientist.com/templates/trackable/display/news.jsp?type=news&o_url=news/display/24841&id=24841 as well. "It strongly suggests that a lot of leads for drug discovery that people have been pursuing for protein aggregation diseases are probably artifacts," Shoichet told The Scientist. The fact that these compounds are not specific and block any protein they come in contact with suggests that "these inhibitors are probably the wrong direction" for drug discovery, Shoichet added. "It's a very important beginning for uncovering therapeutics that can affect these diseases," linkurl:Colin Masters,;http://www.mdhs.unimelb.edu.au/aboutus/staff an Alzheimer researcher at the University of Melbourne, who was not involved in the study, told The Scientist. Master's team has been working with one of the molecules that Shoichet's group tested, clioquinol, and said that this study will help elucidate some unusual inhibiting activity data that Master's group has been trying to reconcile.