Treatment strategies in amyotrophic lateral sclerosis and its mimics

Abstract

1. Symptomatic treatment remains the only way doctors can improve quality of life of patients with amyotrophic lateral sclerosis (ALS), due to the lack of specific treatment. Although many potentially disease course-modifying strategies for ALS have been tested in clinical trials, only riluzole has proven to extend life expectancy marginally. Although symptomatic treatment may be a way to show a doctor’s good intentions, we know little about its efficacy and when it should be started. Evidence based symptomatic treatment would therefore be welcomed by patients and doctors alike. 2. Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the SMN1 gene. The nearly identical SMN2 gene is a disease-modifying gene for both ALS and SMA. We hypothesized that up-regulation of the SMN genes might improve disease course of both SMA and ALS and investigated the up-regulating and/or clinical effects of valproic acid (VPA), an HDAC inhibitor, in cell cultures, an ALS mouse model and in SMA and ALS patients. 3. Multifocal motor neuropathy (MMN) is an immune mediated disease and treated with intravenous immunoglobulins. We investigated whether subtypes of motor neuron disorders might be immune mediated and might benefit from immune-modulating treatment. We performed a national cohort study on MMN in the Netherlands and we investigated the interaction of intravenous immunoglobulins with complement activity in MMN. We performed an RCT on the effects of mycophenolate mofetil in MMN patients on maintenance treatment with intravenous immunoglobulins.