Powering Up Mitochondrial Function to Treat Mitochondrial Disease
Abstract
Topic Area: Here we propose a novel approach to treat mitochondrial disease. Mitochondrial disease is among the Fiscal Year 2015 Peer Reviewed Medical Research Program topic areas and is of substantial relevance to the healthcare needs of US military Service members, Veterans, and beneficiaries. Statement of Problem: Mitochondria are essential cellular organelles responsible for generating most of the energy our body needs. Optimal mitochondrial function is central to health and performance, both physical and intellectual. Mitochondrial disease results from the loss of mitochondrial function and can affect both children and adults. For example, many adults with late-onset mitochondrial disease have been ill their whole lives but went undiagnosed. Others have carried the genetic mutation that causes mitochondrial disease since birth but did not show any symptoms until a severe illness brought them on. Mutations of hundreds of genes cause different types of mitochondrial disease exhibiting a wide range of symptoms, with those affecting the heart (cardiomyopathy) among the most common symptoms. In addition, mitochondrial dysfunction is implicated in a variety of common age-related diseases, including Alzheimer s disease, Parkinson s disease, diabetes, obesity, stroke, and a wide range of cancers. Many US military Service members, Veterans, and beneficiaries suffer from mitochondrial disease or age-related diseases associated with mitochondrial dysfunction. Mitochondrial dysfunction has also been implicated in a broad range of intoxications including those associated with Agent Orange and the Gulf War Syndrome. Currently, there are no effective treatments for mitochondrial disease. Overview: We recently found that a specific cellular signaling pathway is critical in maintaining normal mitochondrial function. Induction of this signaling pathway increases mitochondrial function in cells. Building on these findings and our long-time work in mitochondrial genetics and disease, we propose to activate this specific cellular pathway to improve mitochondrial functions in order to treat mitochondrial disease. We will test our approach in several original preclinical models of mitochondrial disease. These include cells and mice carrying specific mitochondrial and nuclear DNA mutations that model related human mitochondrial diseases, and patient-derived heart cells that model human mitochondrial cardiomyopathy. Impact: Currently, there is no effective treatment for mitochondrial disease, and novel therapies are urgently needed. We expect that our study will demonstrate that activating this cellular signaling pathway is effective in treating mitochondrial disease. If successful, we plan to initiate clinical studies for human mitochondrial disease treatment. Our studies may bring novel therapeutic options for many citizens including those on active duty, Veterans, and their family members who suffer from mitochondrial disease or mitochondrial dysfunction-related diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610400
Entities
People
- Liming Pei
Organizations
- United States Army