N-Amino Peptide Inhibitors of Tau Propagation

Student: Christopher Vallace, 2021-2022

Sponsor: Juan Del Valle, Kamlesh Makwana, Notre Dame

Tauopathies, such as Alzheimer’s Disease, are a category of neurodegenerative disease stemming from dysfunctional microtubule-associated protein tau. Dysfunctional tau stops stabilizing with the microtubules that maintain neuron shape, instead forming toxic aggregates. Tau aggregates disrupt neuronal cell function, leading to cell death and cognitive decline. Currently, treatments are available that ameliorate the symptoms of tauopathies by essentially boosting brain activity as neurons continue to die, however, no treatments exist to target tau aggregates directly and halt neurodegeneration. There is a clear need for better therapeutics in this space. The Notre Dame research team is developing an N-amino peptide inhibitor of tau aggregation designed to bind to and cap tau aggregates to prevent spread of neurodegeneration. As the team tweaks peptide design, I am researching the clinical development of, and investment in, tau therapies to de-risk the path toward clinical trials for this therapeutic.