Despite intensive development efforts, options for treating amyotrophic lateral sclerosis (ALS) remain limited, highlighting an urgent demand for new therapies capable of slowing disease progression. Mounting evidence indicates that motor neuron hyperexcitability and accumulation of cytoplasmic protein aggregates play important roles in ALS pathophysiology.
This Early Feasibility Study (EFS) investigated the effects of multi-site direct current stimulation (multi-site DCS), a novel, non-invasive neuromodulation intervention that can suppress motor neuron hyperexcitability and enhance protein degradation pathways. Pre-clinical studies in SOD1G93A and TDP-43 mouse models have demonstrated reduction in spinal excitability, improvement in motor function, reduction in cytoplasmic protein aggregation and improved survival post-treatment. A non-invasive intervention that reduces hyperexcitability and enhances protein degradation pathways could be impactful as a novel therapeutic approach for slowing ALS disease progression and would be synergistic with pharmacological treatments.
The primary objective of this single-center, open-label EFS was to confirm that the treatment regimen (15 treatments over 6 weeks, alternating between cervical and lumbar stimulation) delivered by an investigational multi-site DCS device (MyoRegulator®) was safe, tolerable and feasible in ALS. Secondary endpoints included ALSFRS-R, ALSAQ-40 and FVC. This trial was carried out at Spaulding Rehabilitation Hospital (Charlestown, MA) with support from the Muscular Dystrophy Association.
Five participants <3 years from diagnosis were enrolled, with one participant withdrawn for reasons unrelated to the intervention. All participants completing treatment were able to successfully complete each session without any serious adverse events, demonstrating good tolerability and safety of the treatments. The perceived level of functioning among participants remained relatively stable over the treatment course as shown by lack of statistically significant change on clinical secondary endpoints. When compared to historical controls, a favorable trend was noted in ALSFRS-R mean monthly decline in treated participants. This EFS demonstrated that multi-site DCS is safe, tolerable and feasible for people with ALS.