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Oxford-Harrington Rare Disease Scholar Award
Development of ATAD3A Peptide Inhibitor as a Potential Treatment for Alzheimer's disease
2022 Vinney Scholar, Harrington Brain Health Medicines Center
Mitochondria is a cellular organelle often referred to as “the powerhouse” because it generates energy fueling cell lifecycle processes. Evidence suggests that mitochondrial damage plays a critical role in the pathogenesis of Alzheimer's Disease (AD), Parkinson's (PD) and rare neurodegenerative diseases, such as Huntington's (HD) and amyotrophic lateral sclerosis (ALS). This makes it a viable target for both small molecule- and peptide-based treatment strategies to prevent or slow neurodegeneration that impairs memory and mobility.
“We know that mitochondrial dysfunction leads to neuropathology in HD and it occurs in early stage AD,” says Dr. Xin Qi, whose laboratory pioneers small molecule mitochondrial enhancers and the use of peptide inhibitors, such as DA1, HV-3, and P110, against mitochondrial dysfunction in various neurodegenerative diseases.
As a 2018 Harrington Rare Disease Scholar, Dr. Qi and team demonstrated efficacy of a small molecule compound, CHIR99021, in patient brain cells and animals with HD to rescue mitochondrial proteostasis and bioenergetics. With support of the Vinney Scholar Award, Dr. Qi is testing a peptide inhibitor aimed at the protein, ATAD3A, to prevent mitochondrial damage in AD.
“Our goal is to develop a target-specific ‘mitochondria medicine' to delay onset of serious neurodegenerative symptoms and slow disease progression,” she explains.
Harrington support has proven invaluable in advancing Dr. Qi's academic science to drug development.
“Our Harrington advisor has engaged a peptide chemist to help us improve medicinal chemistry for subcutaneous delivery,” she says. “We are working to achieve stability and increase half-life—prerequisites for animal safety studies and clinical trials. The project is running well and results are exciting!”