Neurodegenerative motor neuron disorders (MNDs) have devastating effects. Spinal Muscular Atrophy (SMA), for example, is a debilitating and sometimes lethal disease in children. SMA is monogenic, autosomal recessively inherited disorder caused by a loss-of-function mutation of surviving motor neuron 1 (SMN1). SMN2 is an identical copy of this gene and produces abbreviated transcripts without exon 7 though some full transcripts are produced that ameliorate the disease. Previous clinical trials for this disease have not produced consistent results. However, in a recent cross-sectional study, biomarkers for SMA (BforSMA), protein candidates and metabolite markers were identified (Finkel et al., 2012). These markers can be used for clinical assessment, identification of molecular pathways, and may guide response to treatment. Clinical trials of amyotrophic lateral sclerosis (ALS), another motor neuron disorder, have been uniformly disappointing without the benefit of a full understanding of ALS’s mechanisms. Numerous theories attempt to explain ALS’s selectivity for motor neuron degeneration, but none are conclusive. One hypothesis, gem depletion, emerges from the studies of superoxide dismutase 1 (SOD1) transgenic mice that have been discovered to contain low levels of SMN, thereby potentially linking SMA and ALS. Furthermore, SMN1 and SMN2 are seen as risk factors for ALS (Andersen & Al-Chalabi, 2011). Biomarker identification may also help in identifying ALS’s pathogenesis and pathophysiology as it has begun to do for SMA. ALS and SMA may be more similar than previously thought. Both MNDs may interact in a variety of genetic and mechanistic pathways unknown at present. If so, this may serve to link seemingly disparate crippling diseases, and thereby promote efforts by government agencies and pharmaceutical companies to pursue research and development for these “orphan” diseases.
Groden, M. (2015). Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA): A Genetic Linkage?. The Science Journal of the Lander College of Arts and Sciences, 8 (2). Retrieved from https://touroscholar.touro.edu/cgi/viewcontent.cgi?article=1069&context=sjlcas