Portable Neuromodulation Stimulator Therapy Improves Multiple Sclerosis Gait in Longitudinal PoNSTEP Study

Antonella Favit-Van Pelt, MD, PhD

Recently announced data from the PoNSTEP trial showed that treatment with Helius’ Portable Neuromodulation Stimulator (PoNS), a non-implantable, orally applied therapy, resulted in improved gait deficit among patients with multiple sclerosis (MS). The recent study provides the first clinical evidence linking adherence to PoNS Therapy—combining the PoNS device with targeted exercise—to improved gait deficits and sustained therapeutic effects in people with MS 6 months post-treatment.¹

The study comprised of 43 patients with gait deficits from mild-to-moderate MS who underwent 14 weeks of PoNS therapy, including 2 weeks of in-clinic rehabilitation (phase 1), 12 weeks of at-home therapy (phase 2), and a 6-month post-treatment observation (phase 3). During phase 1 and 2, investigators observed statistically significant mean improvement of 5.00 (4.1-5.9; P <.0001) on dynamic gait index (DGI) at week 14 for the 38 participants who completed the treatment protocol.

"The results from this study validate existing evidence of the efficacy of PoNS across clinical data and real-world utilization of the therapy by demonstrating durability of effect as further evidence of its long-term therapeutic benefits,” Antonella Favit-Van Pelt, MD, PhD, chief medical officer at Helius, said in a statement.¹ "The PoNSTEP study marks an important stepstone in further understanding the role of neuromodulation and, consequently, neuroplasticity in gait function rehabilitation. PoNS Therapy’s neuromodulation effect on brain mechanisms of motor control is likely to enhance neuroplasticity and contribute to maintain PoNS therapeutic effect on gait deficit in people with MS."

In 2021, the FDA granted market authorization for the PoNS device as a new therapy for use during physical therapy to treat walking problems in those with MS. The device, intended only as adjunct to a supervised therapeutic exercise program, generates electrical pulses to stimulate nerves in the tongue, and in turn the brain, to treat motor deficits. This nonimplantable device includes a mouthpiece held in place by lips and teeth, as well as a control unit, worn around the neck.

In phase 2 of the PoNSTEP study, there was a 71% adherence rate to the therapy, with results indicating that gait improvement was linearly associated with adherence (r = .345; P = .034). In phase 1, adherence was 89.5% and, consequently, not associated with improvement. During both phases, those with at least 85% adherence to the device improved a mean of 3.7 points (SD, 1.8) compared with mean improvements of 2.0 points (SD, 1.8) for those with less than 85% adherence (P = .008).¹

READ MORE: Differences in Gray Matter Structure May Help Distinguish Multiple Sclerosis From NMOSD

Secondary end points of the study included maintenance of improvement of gait and balance deficit over the 6-month timeframe and clinical global impression of change. Among the 28 participants (70.7%) who completed the 14-week therapy and assessed at 6 months, only 1 demonstrated at least a 30% decline in DGI (95% exact binomial CI, 0.09%-18.4%). Overall, the mean decline in DGI was –4.1 (95% CI, –9.4% to –1.1%; range, –35.7% to 25.0%) with the 95% Cis lower bound showing statistically reliable evidence that the true mean decline was no more than –9.4% (P = .12).

Earlier this year, in an interview with NeurologyLive®, Favit-Van Pelt noted that, "PoNS therapy exerts its effect by promoting neuroplasticity through regular and consistent physical rehabilitation of the impaired function. It relies on the patient’s commitment to perform regularly and consistently the recommended physical therapy program using the PoNS device as instructed. Efficacy is closely related to patients’ consistent at-home utilization during exercise and relaxation tasks for an average of 100 min per day."

Prior to the PoNSTEP study, the PoNS therapy was tested in a number of different studies, including a real-world trial presented at the 2022 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting. There, results revealed that use of the therapy combined with a therapeutic exercise program significantly improvement gait deficit at week 2, the earliest evaluated time point, and at every subsequent time point. At week 14, 58.3% of patients had a Functional Gait Assessment improvement of at least 4 points, surpassing the minimal detectable change for older adults, patients with stroke, and those with neurological disease.²

A 2017 study published in the Multiple Sclerosis Journal-Experimental, Translational and Clinical highlighted the potential of PoNS stimulation to enhance motor performance and working memory in patients with MS. The study, which randomly assigned 14 patients to either active or sham stimulation, revealed significant improvements in sensory organization tests, as well as significant blood oxygen level-dependent signal changes in the left primary motor cortex with PoNS. All individuals improved on working-memory tasks, but only the active group showed increased dorsolateral prefrontal cortex activity.³

REFERENCES
1. Helius Medical Technologies, Inc. Announces First Clinical Evidence of Positive Long-term Therapeutic Effects of PoNS Therapy® on Gait Deficit Improvement in Multiple Sclerosis from the PoNS® Therapeutic Experience Program Study. News release. Helius Medical Technologies. January 22, 2025. Accessed January 22, 2025. http://globenewswire.com/news-release/2025/01/22/3013331/0/en/Helius-Medical-Technologies-Inc-Announces-First-Clinical-Evidence-of-Positive-Long-term-Therapeutic-Effects-of-PoNS-Therapy-on-Gait-Deficit-Improvement-in-Multiple-Sclerosis-from-t.html
2. Helius Medical Technologies, Inc. Presents Poster at the 2022 Consortium of Multiple Sclerosis Centers (“CMSC”) Annual Meeting. News release. Helius Medical Technologies. June 6, 2022. Accessed January 22, 2025. https://ponstherapy.com/news/helius-medical-technologies-inc-presents-poster-at-the-2022-consortium-of-multiple-sclerosis-centers-cmsc-annual-meeting/
3. Leonard G, Lapierre Y, Chen J, Wardini R, Crane J, Ptito A. Noninvasive tongue stimulation combined with intensive cognitive and physical rehabilitation induces neuroplastic changes in patients with multiple sclerosis: A multimodal neuroimaging study. Mult Scler J Exp Transl Clin. 2017;3(1):2055217317690561. doi:10.1177/2055217317690561