Investigating the mechanisms underlying peripheral neuropathy

California Pacific CURRENTS: The online journal of CPMC Research Institute

Research leads to new strategies to preserve nerve function in the elderly

Loss of touch sensation, poor motor nerve function, and in some cases pain, burning or tingling in the feet or hands—these and other symptoms of poor peripheral nerve function commonly afflict the elderly, and can severely impact quality of life, physical functioning, and wellbeing.

Greg Tranah, Ph.D., CPMCRI and San Francisco Coordinating Center (SFCC) scientist, and Adjunct Professor in the Department of Epidemiology & Biostatistics at UCSF, studies mitochondrial dysfunction in age-related illnesses including dementia and Alzheimer’s disease. As mitochondrial dysfunction is a common characteristic of several neuropathies including peripheral neuropathy, Dr. Tranah focused key investigations this year on understanding sensory deficits and neuropathic impairments.

He is among a select group of researchers in the U.S. uncovering how alterations in mitochondrial DNA (mtDNA) play a much greater role than once believed in neurodegeneration and age-related brain illnesses. And while the study of mtDNA is well established, the availability of inexpensive, high-throughput genotyping and DNA sequencing has allowed researchers to examine mtDNA in much larger studies of disease and aging.

One of Dr. Tranah's studies expanded upon this work and examined the influence of inherited and acquired mtDNA mutations on peripheral neuropathies in the elderly. Studying over 2,000 elderly participants from the Health, Aging and Body Composition (Health ABC) cohort, Dr. Tranah and colleagues investigated the role of mtDNA sequence variation on peripheral nerve function. Even though common individual genetic variants were found to play a much smaller role in peripheral nerve functioning than initially hypothesized, groups or aggregates of multiple sequence variants had a stronger impact on motor nerve conduction velocity and amplitude.

“The genetic information coding for mitochondrial protein synthesis and assembly is associated with peripheral nerve function, and may provide insight into new targets for therapies that preserve nerve function in the elderly,” says Dr. Tranah. “Since poor peripheral nerve function strongly correlates with diminished physical functioning, new approaches to safeguarding the mitochondrial DNA governing the integrity of these nerves can help extend physical wellbeing in the elderly and prevent sensory and motor nerve degradation.” New directions in this area of research will see Dr. Tranah and colleagues at the SFCC explore how proportions of normal and mutant mtDNA impact the risk of inherited mitochondrial diseases.