Unfolding Alzheimer's Tau Therapies: Near- and Long-Term Approaches

In this project focused on finding new drug candidates, the aim is to develop small molecules with heightened efficiency at targeting the Alzheimer’s protein tau.

Several naturally occurring compounds from plants have been highlighted as possibly deconstructing tangles of tau-like proteins. In this study, Paul Seidler, PhD, and his team will investigate how well a commercially available dietary supplement, formulated to be highly accessible to the body, slows accumulation of these tangles. The researchers will work with lab models of tau protein accumulation to determine which features of this supplement formulation drive any effects on tau tangling.

Using this information, Dr. Seidler and his group will then synthesize small molecules that bear these effective features and test how well they prevent tau accumulation in tissue samples from Alzheimer’s disease brains. The most effective small molecules will undergo further testing to analyze how their structure influences their activity against tau misfolding.

The overall goal is to identify affordable candidates for dietary supplements or pharmaceuticals that are accessible to the body’s cells and effective against tau-related changes in Alzheimer’s disease.

We leverage neuroactive natural products with known safety records to accelerate discovery. Our team is exploring the use of DHM, a commercially available dietary supplement, and formulations of it with increased solubility and bioavailability. In addition, we are drawing inspiration from DHM to develop novel pharmaceuticals. Our investigations have potential to yield dietary supplements with improved bioavailability with possible near-term commercial availability, and in the long run pharmaceutical-grade medications to target tau pathology associated with AD.

Our team expects to produce a bioavailable formulation of DHM that is scientifically backed and ready for the market. Natural products are an underutilized source of affordable chemicals that can be rapidly deployed to support healthy aging. Few chemicals offer promise to impact the health of aging individuals within the short timeline of the next few years. Our strategy offers a means to rapidly implement innovative dietary supplement formulations of DHM as a chemical tool to promote healthier aging by counteracting age-related protein aggregates that form in the brain.