PathMaker Neurosystems Inc. has announced that it has received Institutional Review Board (IRB) approval to commence enrollments in the U.S. Department of Defense-funded CALM study, which stands for "Controlling Amyotrophic Lateral Sclerosis Motor Neuron Excitability." This trial will evaluate PathMaker’s MyoRegulator device in individuals diagnosed with amyotrophic lateral sclerosis (ALS). The study is set to take place at Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA.
The CALM study (NCT06649955) is designed as a single-site, open-label trial. Its primary objectives are to further assess the feasibility and safety of the MyoRegulator treatment in ALS patients and to gather initial evidence of its efficacy through advanced clinical, neurophysiological, and biochemical endpoints. The trial is being led by Seward Rutkove, M.D., Chair of the Department of Neurology at Beth Israel Deaconess Medical Center and Nancy Lurie Marks Professor of Neurology at Harvard Medical School, along with Courtney McIlduff, M.D., MMSc, Assistant Professor of Neurology at Harvard Medical School and Director of the Multi-Disciplinary ALS Clinic at Beth Israel Deaconess Medical Center.
MyoRegulator Mechanism and Prior Studies
PathMaker’s therapeutic approach utilizes its proprietary multi-site direct current stimulation (Multi-Site DCS) platform. This platform aims to modulate neurons and circuits associated with ALS by suppressing motor neuron hyperexcitability and activating protein degradation pathways. The MyoRegulator device has previously been evaluated in an early feasibility trial for ALS and in three clinical trials focusing on post-stroke spasticity.
The MyoRegulator device delivers a mild electric current to specific parts of the spinal cord and peripheral nerves through disposable electrodes applied to the skin. PathMaker Neurosystems is developing the device for potential at-home use.
Trial Design and Endpoints
The CALM study aims to enroll approximately 15 adults with ALS who have experienced symptom onset within the past two years. Participants will receive treatment three times a week for four weeks and will be followed for up to six months after completing the treatment period.
The primary goals of the study are to assess feasibility, measured by the number of patients completing all treatment sessions at the defined stimulation levels, and safety, evaluated by the frequency and duration of adverse events. Secondary outcome measures include changes in the Revised ALS Functional Rating Scale (ALSFRS-R) scores, a measure of functional disability, and patient-reported assessments of their ability to perform activities of daily living. Additional assessments will include changes in quality of life, muscle strength, lung function, and neuronal excitability.
Executive Perspective
Nader Yaghoubi, M.D., Ph.D., Co-Founder and CEO of PathMaker, commented, “We are pleased to announce IRB approval for the CALM study, which allows us to commence enrollments shortly. Given the mechanisms by which our technology works, we believe our non-invasive platform represents a new treatment modality that will be broadly applicable to ALS.”
Funding and Regulatory Status
This research is supported by the Office of the Assistant Secretary of Defense for Health Affairs, endorsed by the Department of Defense, through the Amyotrophic Lateral Sclerosis Research Program. The MyoRegulator device has been designated by the FDA as a “Breakthrough Device” and is currently limited to investigational use only.
