New research suggests that strategies used to successfully treat spinal muscular atrophy (SMA) may be applied to curb muscle decline associated with aging. The study, conducted by scientists at Ohio State University, found that the survival motor neuron protein, which is present throughout the body and is important for keeping motor neuron cells alive and sending proper signals from the central nervous system to muscles, plays a key role in both SMA and sarcopenia, the age-related loss of skeletal muscle mass and strength.
At the heart of SMA is a gene mutation that leads to reduced levels of the survival motor neuron protein. Gene therapy is among three SMA therapeutics clinically available and has been used to successfully treat children with the disease. Based on what years of SMA research has shown about the importance of the survival motor neuron protein to neuromuscular integrity, Ohio State University scientists are exploring links between the protein and sarcopenia.
Their new study in mice suggests a clear relationship between the survival motor neuron protein and muscle decline with aging. Levels of the protein in the spinal cords and motor neurons of advanced-age mice were 22% and 55% lower, respectively, than the levels in middle-aged mice. These protein drops were accompanied by reduced muscle function.
“We found that SMN protein and aging are related – there is a decline in the protein with age and it correlates with a decline in neuromuscular function,” said Maria Balch, the first author of the study and a postdoctoral scholar in neuroscience at Ohio State’s College of Medicine. “Based on what we know about SMA and therapeutics, we have background in targeting SMN protein – and it’s possible that could be something down the line that could be applied to age-induced neuromuscular decline.”
The Ohio State team found that mice engineered to express higher-than-normal levels of SMN protein had more overall neuromuscular resilience and recovered faster from nerve injury. This raises the possibility that the problem of muscle decline associated with aging could be addressed by coaxing the aging body to produce more SMN protein.
While the researchers speculate that a combination of genetics and behavior are at play in muscle decline associated with aging, their findings offer hope that the problem could be addressed by targeting the survival motor neuron protein. However, the viral-mediated gene therapy currently in the clinic for infants with SMA is not a likely solution for treating sarcopenia in adults as it would require a large amount of virus. Further research is needed to explore alternative treatment options.