Targeting Mitochondrial Energy Metabolism for Symptomatic Improvements in Gulf War Illnesses
Abstract
This Idea Award application will address the overarching challenge in eliminating the health consequences associated with Gulf War Illness (GWI). Specifically, we will focus on dysregulation in the neurological system, including central, peripheral, and neuromuscular. Our scientific objective is to evaluate the efficacy of acetyl-L-carnitine (ALCAR) and alpha-lipoic acid (ALA), two commonly used supplements, in enhancing mitochondrial energy metabolism in the GWI mouse model with the ultimate goal of translating the benefits to the clinics for GWI Veterans. Research on Veterans with GWI, as well as on animal models for GWI, in recent years has pointed to defects in mitochondrial function as one of the root causes of cellular and tissue dysfunctions in the latent phase of GWI. Mitochondria are the power plants inside cells, and energy generated by mitochondria is essential for normal cellular and tissue functions. Defects in the mitochondria lead to tissue degeneration and functional impairments. ALCAR and ALA are important for mitochondrial energy production. Upon absorption, ALCAR is metabolized into L-carnitine, which then brings fatty acids into the mitochondria as the fuel for energy production. ALA, on the other hand, is an important co-factor for several enzymes in the mitochondria; it is also a potent antioxidant. ALCAR and ALA have been used in different basic and clinical research settings for preventing side effects from or risk factors for a number of chronic diseases. Long-term supplementation of combined ALCAR and ALA has been shown to be effective in improving memory and preventing mitochondria decay in old rats and reducing disease severities in mouse models of Parkinson disease and Alzheimer disease. ALCAR supplementation alone has also been effective in reducing depressive disorder in human patients. ALCAR and ALA are easily absorbed in the gastrointestinal (GI) system with well-characterized safety profile and drug absorption, distribution, turnover, and bioavailability data. Pharmaceutical grade ALCAR and ALA are approved in some European countries to alleviate peripheral neuropathy and a number of disorders in elderly patients, whereas in the US they are used as supplements. Because long-term use of ALCAR and ALA have a proven safety and efficacy track record in the clinics, the ultimate applicability of this research is to translate the treatment strategy to GWI clinics without the need for lengthy clinical trials. Since these two agents are readily available in the open market, we expect the timeframe to achieving a patient-related outcome will be a couple years after completion of this project to allow time for a verification phase in GWI clinics.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010232
Entities
People
- Ting-ting Huang
Organizations
- Palo Alto Veterans Institute for Research
- United States Army