Development of effective therapy for sporadic ALS

We appreciate the discussion of hopes and difficulties with gene therapy for Amyotrophic lateral sclerosis (ALS) in the excellent review by Scarrott et al. [1]. The authors point out the molecular and economic problems resulting from a wide variety of genes and mutations in ALS, which necessitate multiple allele-specific constructs. Although non-allele-specific ablation of the endogenous superoxide dismutase-1 (SOD-1) by anti-sense oligonucleotide delivered into the cerebrospinal fluid has a current potential in SOD-1 related disease, gene therapy for the majority of patients with sporadic disease appears to be a hope for the future.

However, sporadic ALS is accompanied by strong inflammation in the affected spinal cord resulting from misfolded proteins, such as fibrillar SOD-1. This inflammation is mediated by macrophages and T and possibly B cells that damage motor neurons by cytokines and phagocytize damaged apoptotic and non-apoptotic neurons [2]. Sporadic patients are heterogeneous, as there are subgroups with different type of inflammation, including Th1, Th17 and B cell type (Fiala and Pellegrini, submitted for publication 2015). Two patients with strong evidence of Th1 inflammatory activation were treated using the antibody to IL-6 receptor α called tocilizumab (Actemra) with strong biochemical and immune effects and apparent slowing of the disease progression [3]. The pre-clinical studies of tocilizumab will culminate in a clinical trial of Actemra that is scheduled to start this year in four centers in USA. Thus, anti-inflammatory therapy as well as gene therapy could together be components of a more effective approach to ALS.

Declaration of interest

The authors state no conflict of interest and have received no payment in preparation of this manuscript.