Trichostatin A and dihydrotestosterone as potential multi-systemic drugs for amyotrophic lateral sclerosis

UnrestrictedAmyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) is a lethal neurodegenerative disease characterized by motor neuron loss, progressive muscle weakness, atrophy and paralysis. ALS is the most common motoneuron disease in human adults, and currently, there is no cure for ALS. Although ALS is a motoneuron disease, non-neuronal cells have been implicated in modulating motoneuron degeneration and disease progression. Because trichostatin A (TSA) and dihydrotestosterone (DHT) have shown beneficial effects on multiple cell types implicated in ALS, we examined their effects as a potential drug in a mouse model of ALS, SOD1 G93A mice.; The treatment of TSA or DHT to early symptomatic SOD1 G93A mice ameliorated muscle atrophy, NMJ denervation, axonal degeneration, and motoneuron death, which are the pathological characteristics found in SOD1 G93A mice. The improved morphology in TSA- or DHT-treated SOD1 G93A mice was accompanied by improved motor functions as well as prolonged lifespan. The beneficial effect exerted by TSA or DHT might be mediated by their potential effects on multiple cell types implicated in ALS. Since ALS is a disease that involves neuronal and non-neuronal cell types, TSA or DHT treatment, which can target multiple cell types, might be an effective strategy to slow motoneuron loss, as well as to improve motor performance that may lead to the improved quality of life for ALS patients