In a layer cake of research labs nestled on separate floors in a remote corner of the Hospital of the University of Pennsylvania, a new use for an existing drug was uncovered. The drug, epothilone D (EpoD), stalled after original tests as a cancer treatment, but Perelman School of Medicine researchers have found it is effective in preventing further neurological damage and improving cognitive performance in a mouse model of Alzheimer's disease (AD). Now, the drug company is starting to enroll AD patients in clinical trials to test the drug.
Translational Research in Action
In the spring of 2011, Penn celebrated the opening of the Smilow Center for Translational Research – a new home for Penn Medicine's emphasis on translating breakthroughs in the lab to clinical therapies for patients. The story profiled here is just one example of such research at Penn.
My colleague Karen Kreeger has written press releases about what the drug is and does, but I'm fascinated by how it came to be. It's not every day that academic researchers go so far beyond identifying a specific target by seeing an agent well into the drug development stages and discovering new uses after its initial clinical testing.
Kurt Brunden, PhD, who spearheads the drug discovery efforts at Penn's Center for Neurodegenerative Disease Research, came to Penn from the pharmaceutical industry, with hopes of progressing the basic research being conducted here and speeding it toward clinical trials. Here, he explains how the process works at Penn, and how teamwork from across the Penn campus has helped make it possible for this academic drug discovery program to be a success.
As Dr. Brunden notes, academia can play a complementary role – alongside the typical research and development might of the pharmaceutical industry -- in helping bring much-needed therapeutics into clinical trials as quickly as possible.
Zhang B, Carroll J, Trojanowski JQ, Yao Y, Iba M, Potuzak JS, Hogan AM, Xie SX, Ballatore C, Smith AB 3rd, Lee VM, & Brunden KR (2012). The microtubule-stabilizing agent, epothilone d, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (11), 3601-11 PMID: 22423084
Brunden KR, Zhang B, Carroll J, Yao Y, Potuzak JS, Hogan AM, Iba M, James MJ, Xie SX, Ballatore C, Smith AB 3rd, Lee VM, & Trojanowski JQ (2010). Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30 (41), 13861-6 PMID: 20943926