NIH Awards $6.9 Million to Advance Potential Alzheimer’s Disease Treatment

Alzheimer’s disease is characterized by abnormal deposits of two types of protein in the brain: amyloid beta (Aβ) and tau. The only currently available disease-modifying treatments for Alzheimer’s, lecanemab (Leqembi™) and donanemab (Kisunla™), target Aβ deposits in the brain. Notably, there are currently no approved therapies that target pathological tau. In mice, the researchers found that CNDR-51997 was able to reduce both Aβ plaques and tau pathology in the brain.

In addition to Alzheimer’s there are several other diseases characterized by tau pathology, such as frontotemporal lobar degeneration, progressive supranuclear palsy, corticobasal degeneration, Pick’s disease, traumatic brain injury and chronic traumatic encephalopathy (CTE). The researchers believe that their compound could not only be a future treatment for Alzheimer’s, but also for these other related diseases, collectively called tauopathies.

“Our findings that CNDR-51997 reduces both Aβ plaques and tau inclusions in mouse models suggest that the compound holds considerable promise for Alzheimer’s disease. However, there is also a great unmet need for disease-modifying drugs for the other tauopathies,” said Brunden, a research professor in the Perelman School of Medicine and director of drug discovery at Penn’s Center for Neurodegenerative Disease Research. “The potential of CNDR-51997 to address tau-related diseases beyond Alzheimer's is another important aspect of its therapeutic promise.”

One of the functions of tau is to stabilize microtubules, dynamic tube-like structures that help give cells their shape. In neurons, microtubules play an important role in axonal transport, a process in which proteins and other cellular constituents are distributed to different parts of the long axonal extensions that are involved in brain function.

In Alzheimer’s disease and other tauopathies, tau becomes detached from microtubules, which causes them to become disorganized. This leads to axonal transport deficits and neuronal loss. In preclinical studies, the new compound CNDR-51997 was able to correct these imbalances, ultimately reducing both Aβ and tau pathologies.

“This is a unique compound with desirable properties, and Dr. Brunden and I are grateful to the NIA for their continued support and the opportunity to develop this compound further through IND-enabling studies, which if successful, will lead to an IND submission,” said Ballatore.