ALS patients lose significant muscle mitochondrion causing muscle degradation and muscular atrophy. However, as the figure to the right demonstrates, treatment with PGC-1alpha reduces muscle degradation suggesting a therapy for improving quality of life, but not survival, for ALS patients.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive, fatal, adult-onset neurodegenerative disorder characterized by loss of motor neurons and degeneration of skeletal muscle. Approximately 300,000 people are affected by ALS worldwide. Although scientists have not found a cure for the disease, a team of researchers from San Diego, California have found a possible lead for a way to alleviate the muscle degeneration that makes the end of life for ALS patients so painful.
The study, Elevated PGC-1alpha Activity Sustains Mitochondrial Biogenesis and Muscle Function Without Extending Survival in a Mouse Model of Inherited ALS (Sandrine Da Cruz, Philippe A. Parone, et al., May 2012), looked at the effects of increased transcriptional coactivator PGC-1alpha on SOD1 mutant mice. PGC-1alpha exerts control over cellular metabolism, specifically mitochondria angiogenesis and biogenesis. The SOD1 mutation causes mitochondrion toxicity that models ALS. The researchers found that by increasing levels of PGC-alpha1, muscle degradation was reduced.
Mitochondrion density is significantly reduced by ALS, however as the picture above demonstrates, comparing SOD1-mutant mice saw significant increases in skeletal muscle mitochondrion density when treated with PGC-1alpha.Vascular endothelial growth factor (VEGF) levels were also raised by the PGC-1alpha. The alleviation of muscle degradation resulted in the increased endurance and voluntary physical activity (distance covered in an open field) in the PGC-1alpha treated mice. The results can be seen below.
PPG-1alpha does not alter the pathogenesis of ALS, it simply reduces the effect of mitochondrion toxics that are released in ALS patients. Unfortunately then, raising PGC-1aplha levels in SOD1-mutant mice did not prevent the motor neurons from being degraded. Thus, PGC-1alpha worked on preventing degradation to the muscular system, but not the terminal nervous system degradation. As the figure below demonstrates, survival duration was not increased by the PGC-1alpha.
This study is significant because it introduces PGC-1alpha as a potential therapy for increasing the quality of life for ALS patients by maintaining muscle function. Unfortunately, PGC-1alpha does not prevent neuron degradation or increase survival duration after onset of ALS. However, it means that Lou Gehrig could have continued playing baseball for a few more months.