Drugs Target Tau Tangle Formation: News from AAIC

Research on epithilone D, an investigational drug targeting the formation of tau tangles in Alzheimer’s disease, was presented at the 2012 Alzheimer’s Association International Conference in Vancouver, British Columbia.

Although many new drugs in the pipeline to treat Alzheimer’s disease (AD) are focused on preventing the formation of beta amyloid plaques, other drugs in development are targeting another suspected villain in AD progression: the tau protein.

Tau proteins are primarily found in the neurons of the central nervous system. They stabilize microtubules in the cytoskeleton of cells, and when tau malfunctions, microtubules break, causing aggregates of tau proteins called neurofibrillary tangles to form. These deposits, also known as tau tangles, have been observed in patients with AD.

It is still unknown whether tau tangles play a causative role in AD, or if they have a more peripheral role in disease progression.

A drug focused on stabilizing microtubules to prevent these neurodegenerative tangles recently started Phase 1 clinical trials, according to research presented by Penn Medicine at the 2012 Alzheimer’s Association International Conference.

The anti-tau medication, developed in partnership with Bristol-Myers Squibb, is called epithilone D (EpoD). In animal models, the drug improved neuron function and cognition and was also effective in decreasing tau pathology. Scientists from the Perelman School of Medicine at the University of Pennsylvania, led by first author Bin Zhang, MD, PhD, senior research investigator, and Kurt R. Brunden, PhD, senior author, director of Drug Discovery at the Center for Neurodegenerative Disease Research, believe that a drug such as EpoD could increase microtubule stability and help improve nerve cell function in AD and other diseases where tangles form in the brain.

“The drug effectively hits a tau target by correcting tau loss of function, thereby stabilizing microtubules and offsetting the loss of tau due to its formation into neurofibrillary tangles in animal models, which suggests that this could be an important option to mediate tau function in Alzheimer’s and other tau-based neurodegenerative diseases,” said John Trojanowski, MD, PhD, professor of pathology and laboratory medicine in the Perelman School of Medicine at the University of Pennsylvania, in a press release.

The key to EpoD’s therapeutic benefits may lie in the dosage given to subjects—the doses of EpoD that resulted in improvements in learning and memory in mice models were much lower than had previously been used in Phase II clinical testing of EpoD in cancer patients.

In this video, Dr. Brunden discusses the drug’s use in animal models: