Results establish direct linkage between overexpression of NKCC1, a neuronal Na-K-Cl cotransporter, and emergence of spasticity
- Results establish direct linkage between overexpression of NKCC1, a neuronal Na-K-Cl cotransporter, and emergence of spasticity
- Investigators showed that NKCC1 is reduced after application of a novel form of non-invasive stimulation referred to as DoubleStim™
PARIS and BOSTON, Feb. 8, 2019 /PRNewswire/ -- PathMaker Neurosystems, a pioneering clinical-stage bioelectronic medicine company, announced today a publication in the Journal of Physiology of results from a pre-clinical study that measured the long-term effects of repeated stimulation with a novel form of non-invasive stimulation to reduce spasticity in mice with spinal cord injury (SCI). Spasticity is a chronic condition characterized by painful muscle contractions and is common in patients with many neuromuscular disorders including SCI, stroke, traumatic brain injury, cerebral palsy, and multiple sclerosis.
The paper, “Repeated anodal trans-spinal direct current stimulation results in long-term reduction of spasticity in mice with spinal cord injury,” had as senior author, Dr. Zaghloul Ahmed, Professor and Chairman, Department of Physical Therapy and Professor, Center for Developmental Neuroscience, CUNY and Scientific Founder of PathMaker Neurosystems. Results from this NIH-funded study demonstrated that following 7-day treatment with anodal tsDCS combined with peripheral nerve stimulation, referred to as “DoubleStim™” treatment, mice with SCI experienced long-term reduction in spasticity, increased rate-dependent depression in spinal reflexes, and improved ground and skill locomotion. Additionally, pharmacological, molecular and cellular evidence uncovered a novel mechanism involving Na-K-Cl cotransporter isoform 1 (NKCC1) that mediates the long-term effects of repeated DoubleStim treatment and establishes a direct relationship between down-regulation of NKCC1 by DoubleStim and the reduction of spasticity.
“These data are very exciting and support the application of next-generation non-invasive interventions to improve the treatment of spasticity,” commented Dr. Ahmed. “Our previous published work established that application of this novel modality for short periods of time to mice with SCI led to an instantaneous reduction in spasticity. This new study demonstrated that DoubleStim not only contributed to a long-term reduction in spasticity but mediated its effects through a novel mechanism that downregulates NKCC1.”
“This fundamental paper is the first to establish a direct link between the emergence of spasticity and overexpression of a specific neuronal co-transporter responsible for maintaining chloride gradient,” said Nader Yaghoubi, M.D., Ph.D., President and Chief Executive Officer of PathMaker Neurosystems. “We now not only have a target for therapeutic intervention, but through the impressive work of the investigators, have demonstrated the mechanism by which our MyoRegulator® device exerts its therapeutic effects in the treatment of spasticity.
About Spasticity
Spasticity is a chronic condition characterized by painful muscle contractions and is common in patients following stroke, spinal cord injury, traumatic brain injury, cerebral palsy, multiple sclerosis and other neurological disorders. It affects an estimated 12 million people worldwide. Current treatments of the disorder include pharmacological agents, botulinum neurotoxin injections and intrathecal baclofen, which are often costly and result in undesired side-effects.
About MyoRegulator® and DoubleStim™ Technology
The MyoRegulator system is a microprocessor-controlled device that uses PathMaker’s patent-protected DoubleStim technology to deliver synchronized stimulation at two sites along the neural axis via two pairs of disposable skin-surface electrodes. Through precisely sequenced and targeted multi-site stimulation directed at the spinal outflow and peripheral nerve leading to the muscle of interest, this proprietary approach modulates neural activity to suppress hyperexcitable spinal neurons involved in spasticity. Clinical results from a recently completed U.S. study at Northwell Health evaluating the effect of MyoRegulator treatment on post-stroke spasticity were presented at the Society for Neuroscience meeting (San Diego) in November 2018, and the ESC Heart and Stroke meeting (Berlin) in January 2019. MyoRegulator is an investigational medical device and is limited by U.S. Federal law to investigational use only.
About PathMaker Neurosystems
PathMaker Neurosystems is a clinical-stage bioelectronic medicine company developing breakthrough non-invasive systems for the treatment of patients with chronic neuromotor conditions. With offices in Boston (U.S.) and Paris (France), we are collaborating with world-class institutions to rapidly bring to market disruptive products for treating spasticity, paralysis and muscle weakness. More than 48 million patients in the U.S., Europe and China suffer disabilities due to stroke, cerebral palsy, multiple sclerosis, spinal cord injury, traumatic brain injury, Parkinson’s disease and other neurological disorders. At PathMaker, we are opening up a new era of non-invasive neurotherapy for patients suffering from chronic neuromotor conditions. For more information, please visit the company website at www.pmneuro.com.
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