Remotely supervised transcranial direct current stimulation for slowing disease progression in amyotrophic lateral sclerosis (ALS)

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PROJECT SUMMARY ALS affects as many as 30,000 individuals in the United States, with 5,600 new cases diagnosed each year. Riluzole and edaravone, the only drugs approved by the U.S. FDA for ALS, slow ALS progression; however, they do not demonstrate marked improvement in ALS symptoms and increase survival time only by a few months. Hence, most of the care is centered on patient support and symptom management, making rehabilitation an integral aspect for slowing disease progression, prolonging life span and increasing quality of life. Our long-term goal is to develop neuromodulation therapies for easy clinical management of ALS. Transcranial direct current stimulation (tDCS) has been increasingly explored as a promising neuromodulatory tool to prime motor function in several neurological disorders. Despite the emerging importance of cortical dysfunction as a pathophysiological biomarker in disease progression, the study of tDCS in ALS is limited. Here we propose a novel mechanism using remotely supervised tDCS (RS-tDCS) to target hypoexcitable neural pathways to preserve motor function in individuals with ALS. Due to its low risk, ease of use, and portability, tDCS is a candidate neuromodality to be administered in a home-based environment with remote supervision from qualified personnel. Remote supervision would ensure that the stimulation is delivered optimally in the comfort of a patient’s home, reducing burden on patients and caregivers to travel to the clinic or research facility and encourage protocol adherence. We aim to investigate the effectiveness and feasibility of long-term RS-tDCS in individuals with ALS. In a delayed-start design, 38 participants with ALS will be randomized into remotely supervised tDCS or delayed-start control group. The intervention group will receive 24 weeks of anodal tDCS (3 times/week; 72 sessions). The delayed-start group will first receive sham tDCS for 12 weeks followed by a switch to anodal tDCS for 12 weeks. Aim 1 will investigate the safety and feasibility of long-term treatment with anodal RS-tDCS in ALS. Aim 2 will determine the effects of 24-weeks of RS-tDCS on disease progression in individuals with ALS, using the ALS Functional Rating Scale (ALSFRS-R) and other clinical outcomes. As a secondary aim, we will explore the effectiveness of RS-tDCS on upper and lower motor neuron mechanisms in individuals with ALS, quantified using transcranial magnetic stimulation and peripheral nerve stimulation. Successful completion of this project will trigger future studies that will test the clinical translation of tDCS as a home-based neuromodulatory adjuvant to slow disease progression in ALS and create a paradigm shift in the clinical management of ALS.