Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease that affects motor neurons of the spinal cord and brain. While there are currently two FDA-approved small molecule drugs and one ASO for ALS, existing treatments are limited in their impact on disease progression and survival. There is tremendous unmet clinical need for novel approaches to slowing ALS disease progression. _x000D_
This Early Feasibility Study (EFS) investigated the effect of a novel, non-invasive neuromodulation treatment to suppress motor neuron hyperexcitability and enhance protein degradation pathways in participants with ALS, which may slow ALS disease progression. This technology is based on multi-site direct current stimulation (multi-site DCS), which combines trans-spinal DCS (tsDCS) with peripheral DCS (pDCS) to modulate neural circuits. In pre-clinical ALS models, we have demonstrated reduction in spinal hyperexcitability, improvement in motor function, reduction in protein aggregation and increase in survival with stimulation. A non-invasive neuromodulation intervention that reduces hyperexcitability and enhances protein degradation pathways could be impactful as a novel therapeutic approach to ALS and could be synergistic with pharmacological treatments._x000D_
The primary objective of this single-site, open-label EFS in five participants with ALS was to confirm that the treatment regimen (15 treatments over 6 weeks, alternating between cervical and lumbar stimulation) was safe, tolerable and feasible in ALS. Secondary endpoints included ALSFRS-R, ROADS and ALSAQ-40. This trial was carried out Spaulding Rehabilitation Hospital (Charlestown, MA) with the support of the Muscular Dystrophy Association._x000D_
Four participants with ALS were enrolled and completed treatment, while a fifth participant was enrolled but withdrawn for reasons unrelated to the intervention. All participants who completed treatment were able to successfully complete each session without presenting any serious adverse events, demonstrating good tolerability and safety of the treatments. The perceived level of functioning among participants remained relatively stable over the course of treatment as shown by lack of statistically significant change on the ALSFRS-R and ROADS. When compared to historical controls (PRO-ACT), a favorable trend was noted in ALSFRS-R mean monthly decline in treated subjects. This EFS demonstrated that this intervention is safe and tolerable in ALS.