BOSTON, MA and PROVIDENCE, RI, Oct. 06, 2026 (GLOBE NEWSWIRE) — PathMaker Neurosystems Inc. (“PathMaker”), a clinical-stage neurotechnology company developing a breakthrough non-invasive treatment for Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig’s disease), today announced the publication of a peer-reviewed study that, for the first time, demonstrates that the Company’s non-invasive multi-site direct current stimulation (Multi-Site DCS) technology can significantly reduce toxic TDP-43 protein aggregates inside motor neurons of an ALS mouse model. The paper, “Multi-site Anodal Direct Current Stimulation Preserves Motor Function and Modulates Key Cellular Pathways in TDP-43 and SOD1 Mouse Models of ALS,” appears in Neuromodulation, the official journal of the International Neuromodulation Society, and is available online at https://authors.elsevier.com/a/1nuPt3uwDfvcOw. The study was led by senior author Dr. Zaghloul Ahmed, Professor of Neuroscience and Motor Control and Chair of the Department of Physical Therapy/Program in Neuroscience at CUNY College of Staten Island, and Scientific Founder of PathMaker.

TDP-43 protein pathology is a defining molecular feature of ALS. Cytoplasmic accumulation of misfolded and phosphorylated TDP-43 is found in motor neurons in approximately 97% of ALS cases, where it is believed to drive neurotoxicity and accelerate disease progression. Reducing TDP-43 aggregation is regarded as a critical therapeutic goal in ALS, but has remained out of reach. Despite its central role in the disease, no approved therapy and no neuromodulatory intervention to date have demonstrated the ability to reduce these toxic protein aggregates.

This landmark study represents the first demonstration that a non-invasive form of neuromodulation can reduce TDP-43 protein aggregates in the cytoplasm of spinal cord motor neurons. Following 4 weeks of stimulation (3 times per week) with Multi-Site DCS, a statistically significant 76% reduction in the number of TDP-43 protein particles per motor neuron was found in stimulated vs. unstimulated TDP-43 mice. This was accompanied by improvements in motor function and preservation of motor neuron size in stimulated mice. Stimulated mice also showed significantly increased expression of HSP70, a molecular chaperone involved in clearing misfolded proteins. The study also demonstrated that the Multi-Site DCS configuration produced robust suppression of spinal motor neuron excitability, consistent with the technology’s design. In the SOD1-G93A model, the study replicated previously published findings, with stimulated mice maintaining significantly better motor performance than unstimulated controls across multiple assessments.

“For the first time, we have shown that our non-invasive Multi-Site DCS technology can reduce toxic cytoplasmic TDP-43 protein aggregates in spinal motor neurons,” said Nader Yaghoubi, M.D., Ph.D., Co-Founder and Chief Executive Officer of PathMaker Neurosystems. “TDP-43 aggregation and motor neuron hyperexcitability are increasingly understood to reinforce each other in a cycle that accelerates ALS progression. This study demonstrates that Multi-Site DCS can intervene on both sides of that cycle, suppressing spinal motor neuron excitability while simultaneously reducing toxic TDP-43 protein accumulation. With our second ALS clinical trial now nearing full enrollment, we are building the clinical evidence base to bring this therapy to people with ALS.”

PathMaker’s Multi-Site DCS technology is the basis of the Company’s MyoRegulator® device, which has received FDA “Breakthrough Device Designation” for the treatment of ALS and is now being utilized in the U.S. Dept. of Defense-funded CALM trial in ALS (NCT06649955).

About PathMaker Neurosystems Inc.
PathMaker Neurosystems is a clinical-stage neurotechnology company developing a breakthrough non-invasive approach to the treatment of amyotrophic lateral sclerosis (ALS). More than 34,000 people in the U.S. and 350,000 people worldwide are estimated to suffer from ALS. PathMaker is collaborating with world-class institutions to develop and bring to market first-in-class products for treating ALS and other neurological disorders with very high unmet medical need. The MyoRegulator® platform is based on PathMaker’s proprietary technology for multi-site direct current stimulation (Multi-Site DCS). MyoRegulator® has received “FDA Breakthrough Device Designation” for the treatment of ALS by the U.S. Food and Drug Administration (FDA). MyoRegulator® and MyoRegulator® ALS are investigational medical devices and are limited by Federal law to investigational use only. For more information, please visit the company website at www.pmneuro.com.


Source: PathMaker Neurosystems Inc.
Media contact: PathMaker PR
(617) 693-7555
partnering@pmneuro.com

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