Testing a Mitochondria-Targeting Compound in Alzheimer's Disease

The study aim is to assess whether a compound that supports healthy mitochondrial stress responses offers benefit in Alzheimer’s disease.

Mitochondria are best known for packaging energy into a usable form for the cell, but they also are emerging as potential very early markers of Alzheimer’s disease–related changes. These indispensable cell structures show these changes sometimes decades before dementia begins to manifest.

Qi Wang, PhD, and her colleagues hypothesize that preventing or repairing this damage might in turn inhibit progression of Alzheimer’s disease. To assess this idea, they plan to use a compound called 9-TB, which shows signs of supporting healthy stress responses in mitochondria. They will test the compound in a lab model of Alzheimer’s disease, including both sexes to determine whether there are sex-based differences in responses.

Following this set of studies, Dr. Wang and her colleagues will analyze how cells respond to 9-TB–related improvements in mitochondrial function. They will assess the cell response at several levels, from gene activity to protein production and location in the cell, known as a multiomics analysis. This work is expected to highlight candidate genes involved in these beneficial responses that Dr. Wang and her coworkers will further assess computer-based and molecular lab studies, including a simulation of how 9-TB might interact in humans to produce beneficial effects.

Dr. Wang and her colleagues ultimately aim to set the stage for phase I clinical studies of drug candidates that generate this healthy mitochondrial stress response. These effects likely would involve several factors in Alzheimer’s disease development, and the group believes any candidates would be poised to be multi-targeting treatments for the condition.

Alzheimer’s Disease is now recognized as a multifactorial and heterogeneous disease, as genetic, biological and environmental factors all contribute to its pathogenesis. Defects in mitochondria proceed the onset of dementia by decades and are involved in multiple aspects of AD pathogenesis. My proposal aims to activate the beneficial mitochondrial stress response pathways to restore mitochondrial function and modulate metabolic homeostasis, which may serve as a promising multi-targeting treatment for Alzheimer’s Disease.

My proposed study will assess the therapeutic efficacy, long-term tolerability and potential toxicity of a non-antimicrobial mitochondrial stress response activator as a potential treatment for Alzheimer’s Disease. Moreover, with the existing human databases, I will evaluate the possibility of translating the observed therapeutic effects into human patients.
If successful, my results will provide key insights to the field of neurodegenerative disorders and set the stages for Phase I clinical studies.