Filling Drug Discovery Niche, Penn Team Helps Move Alzheimer’s Drug Into Clinical Trials

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.

While press releases describe what the drug is and does, it’s fascinating to learn 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.

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Research Update on Alzheimer’s Disease Drug Discovery Efforts

Penn’s Drug Discovery team in the Center for Neurodegenerative Disease Research has been hard at work, since identifying and testing a class of drug last year that is able to enter the brain in an animal model of Alzheimer’s disease, where it stabilizes degenerating neurons and improves memory and learning.

A promising update on the research is posted today on the Penn Medicine News site:

A study published this week in the Journal of Neuroscience shows that the compound epothilone D (EpoD) is effective in preventing further neurological damage and improving cognitive performance in a mouse model of Alzheimer’s disease (AD). The results establish how the drug might be used in early-stage AD patients.

Investigators from the Perelman School of Medicine at the University of Pennsylvania, led by first author Bin Zhang, MD, PhD, senior research investigator, and senior author Kurt R. Brunden, PhD, Director of Drug Discovery at the Center for Neurodegenerative Disease Research (CNDR), administered EpoD to aged mice that had memory deficits and inclusions within their brains that resemble the tangles formed by misfolded tau protein, a hallmark of AD. In nerve cells, tau normally stabilizes structures called microtubules, the molecular railroad tracks upon which cellular cargo is transported. Tangles may compromise microtubule stability, with resulting damage to nerve cells. A drug that could increase microtubule stability might improve nerve-cell function in AD and other diseases where tangles form in the brain.

Read more on the research via the Penn Medicine News press release, and in an article by AFP.

ALS and FTLD on Same Spectrum of Disease

Through years of research, we’re finding that motor neuron diseases share some of the same pathology as cognitive disease.

Watch as Leo McCluskey, MD, MBE, associate professor of Neurology and medical director of Penn’s ALS Center, explains how Amyotrophic lateral sclerosis (ALS)  shares similar disease causes with another neurodegenerative disease – Frontotemporal Lobar Degeneration (FTLD), and what this means for patients with both ALS and FTLD.


For more information on ALS, visit Penn’s ALS Center, a certified ALS Association Center, or the ALS Association.