UCLA researchers in the Department of Chemistry and Biochemistry have developed novel therapeutics for Alzhiemer’s Disease and other tauoapathies.
BACKGROUND:
Alzhiemer’s Disease (AD) is a severe neurodegenerative disease characterized by deterioration of the brain cells and loss of multiple cognitive functions. Although AD is the most prevalent form of dementia, there are limited treatments to alleviate symptoms and none that halt its progression. Histological hallmarks of AD include plaques of amyloid beta and neurofibrillary tangles of tau. In AD, aggregation of amyloid beta is thought to occur at the earliest stages of the disease, and is linked to subsequent aggregation of tau, which in turn correlates with cognitive decline. Cross-seeding between amyloid beta and tau is a proposed mechanism of disease progression. Inhibitors that disrupt the interaction of amyloid beta and tau, or prevent aggregation of either, could be used to treat or prevent AD and other tauopathies.
INNOVATION:
UCLA researchers led by Prof. David Eisenberg reported novel peptide-based inhibitors that can be used to treat or prevent Alzhiemer’s Disease and other tauoapathies by reducing amyloid beta and/or tau aggregation and toxicity of already-aggregated species. To prevent aggregation of toxic peptides, the inhibitors can bind to the ends of growing fibrils and halt fibril growth. Dr. Eisenberg’s group developed a panel of inhibitors targeting different polymorphs of aggregated tau/amyloid beta and showed successful inhibition of aggregation of pathological fibrils in ten different donors with four different tauopathies. Furthermore, the peptide-based inhibitor was engineered to encode cell-penetrating sequences that allow improved delivery of inhibitors across the cell membrane, and different derivatives of the inhibitor as well as its truncated form were created to improve metabolic stability and efficacy.
POTENTIAL APPLICATIONS:
• Novel inhibitor that prevents neurodegeneration by blocking the seeded spread of Tau aggregation
• Novel therapeutics for AD and other tauoapathies by inhibiting aggregation of both amyloid beta and Tau
• Imaging agents for AD and other tauopathies
ADVANTAGES:
• Targeted binding to the end of tau and amyloid beta fibrils to inhibit fibril growth
• Improved cellular and CNS delivery with peptide engineering
DEVELOPMENT-TO-DATE:
This invention has been developed and tested in samples from ten different donors with four different tauopathies.