Do We Have a Channel Solution for ALS?

Abstract

Amyotrophic lateral sclerosis (ALS) is a dreadful degenerative disorder, characterized by rapidly progressing weakness causing respiratory impairment and death, in spite of moderate benefits from non-invasive ventilation, gastrostomy, riluzole treatment and multidisciplinary care (Andersen et al., 2012). Over the years a large of number of drugs have been tested to deal with this disorder, but all trials have been negative except for riluzole. We can observe that different strategies have been explored in the past, from immunosuppression to neuroprotection, from nerve growth factors to antiglutamatergic compounds (de Carvalho et al., 2005). Threshold tracking has been used to investigate axonal excitability in peripheral nerve motor axons in ALS (Vucic and Kiernan, 2006). Increased persistent Na+ conductance and reduced K+ conductance have been described (Vucic and Kiernan, 2006), which tend to become more marked with disease duration and may be a predictor of survival (Cheah et al., 2012). More recently, it has been suggested that motor neurons have an abnormal function of the membrane ion channels, in ALS (Devlin et al., 2015). These observations have opened a new window of opportunity in clinical trials for ALS, for testing drugs that modulate ion channels in order to stabilize membranes.