Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA) are two poorly understood Motor neuron diseases. Both diseases eventually prove fatal and their complex pathogenesis makes them difficult to treat. We reviewed the current literature to produce a comprehensive but succinct guide to ALS and SMA for the undergraduate. We review the genetics, aetiology and pathogenesis to identify similarities and differences between the two diseases. This knowledge was then used to identify and analyses current and possible future treatments. For ALS, Riluzole is currently the best, and only, licensed treatment as it increases life-expectancy by 2 to 3 months. It however only treats the symptoms. Treatments based on Vascular Endothelial Growth Factor (VEGF)’s effects on glutamate controlled calcium channels may prove beneficial in the future, as may recombinant human Insulin like Growth Factor-1 (rhIGF-1) if administration methods are improved. Because of the “gain of function” nature of ALS, prophylactic strategies involving anti-oxidant vitamins are unlikely to prove effective. Additionally, we propose a widespread involvement of Valosin Containing Protein in ALS pathogenesis. Treatment of SMA focuses mainly on raising cytosolic Full Length Survival Motor Neuron protein (FL-SMN) levels, primarily through Histone Deacetylase inhibitors, such as valproic acid, hydroxyurea and phenylbutyrate. These have shown modest benefit but significant side effects. Thyrotropine Releasing Hormone (TRH) and beta-2 adrenoceptor agonists have also been trialled, with few side effects. SMA is also a key target for gene therapy. Finally, Stem cell technology promises a cure for both conditions but, in reality, is many challenging years away from clinical application.
|Journal||Journal of Young Investigators|
|Publication status||Published - 2012|