Exploring spinal muscular atrophy for answers to the motor neuron loss of sarcopenia

Arnold_Image_RTF"As humans reach their thirties, their muscles begin to atrophy as a normal part of aging, a process that speeds up during the eighth decade of life. Traditionally physicians thought that this process, known as sarcopenia, was rooted in the muscle fibers and problems with their regeneration," explains W. David Arnold, MD. "But now we suspect that the loss of motor neurons plays a more significant role in the gradual decline of muscle than previously thought."

Dr. Arnold has been studying spinal muscular atrophy (SMA), a neurodegenerative disorder that leads to early motor neuron loss in patients, with the support of the Rehabilitation Medicine Scientist Training Program, a K12 award from the National Institutes of Health. In researching the mechanisms and progression of this disease, he realized that some features of SMA resemble accelerated aging.

"As motor neuron loss occurs in SMA, it burns through the forest of neurons and it takes out a lot of the trees," Dr. Arnold says. "But the trees that are left are somehow able to survive the fire and compensate for those that are lost. However, the remaining neurons have to do more work, and with subsequent losses of motor neurons, patients notice more substantial declines in their strength and muscle mass."

Dr. Arnold is now following up on this hypothesis both to understand sarcopenia and to look for therapies to improve muscle mass and slow age-related declines. "I am carrying out longitudinal studies of the peripheral nervous system in mice, looking for the primary source of muscle loss. In addition, my team has discovered a protein that, when upregulated, could slow motor neuron loss and facilitate repair. We are currently testing that molecule in mice as a possible therapeutic."