Remepy, a pioneer in Hybrid Drugs™, today announced the publication of new mechanistic findings in npj Parkinson’s Disease (Nature Portfolio). The study provides insight, for the first time, into how Hybridopa™, Remepy’s Hybrid Drug for the treatment of Parkinson’s disease, may enhance the motor improvements previously observed and reported in Remepy’s Phase IIa trial, through multimodal digital interventions, that combine evidence-based training activities with neuroscience-informed tools aimed at promoting brain plasticity.
The publication builds on Remepy’s Phase IIa clinical and neuroimaging findings recently published in Brain Communications, which showed significant improvements in motor and non-motor outcomes in levodopa-treated patients receiving Hybridopa™ compared with levodopa and a placebo app, alongside measurable changes in brain networks involved in movement and mood regulation. The newly published findings extend this evidence by adding a complementary neuroimaging approach using diffusion tensor imaging (DTI), which assesses changes in white matter structure rather than brain function alone. Together, the two studies provide converging functional and structural evidence that Hybridopa™ engages motor-related brain circuits associated with the observed clinical improvements.
“Our Phase IIa trial showed that Hybridopa™ delivers meaningful clinical improvements for people living with Parkinson’s disease,” said Or Shoval, Co-Founder and Co-CEO of Remepy. “This publication helps explain the neural mechanisms underlying those effects. We demonstrate, for the first time, that combining levodopa with precisely structured, personalized, multimodal digital interventions is associated with measurable changes in brain structure and function that align with improved clinical outcomes. This mechanistic insight supports the development of a first-in-class Hybrid Drug for Parkinson’s disease.”
The research was conducted in collaboration with Reichman University, highlighting a strong industry–academic partnership in translational neuroscience.
“Parkinson’s disease involves more than dopamine deficiency. It reflects dysfunction across distributed brain networks,” said Prof. Amir Amedi, Chief Science Officer, Remepy and a professor at Reichman University. “Our findings suggest that a structured, multimodal approach engaging motor, cognitive, emotional, and sensory systems may help modulate these networks and promote neuroplastic changes that complement pharmacological treatment.”
“The combined clinical and mechanistic evidence, supported by advanced imaging techniques and rigorous analysis, strengthens the scientific foundation for Remepy as it prepares to initiate a global Phase III trial of Hybridopa™ later this year,” added Dr. Michal Tsur, Co-Founder and Co-CEO of Remepy. “Together, these findings support a shift in Parkinson’s treatment toward integrated approaches that combine pharmacological therapy with structured, system-level digital interventions. We now have a much deeper understanding of the effects of combining structured, non-pharmacological interventions with levodopa. This growing body of clinical and mechanistic evidence, supported by advanced imaging techniques and rigorous analysis, is what motivates us to advance Hybridopa™ into Phase III later this year.”
Using three different types of brain scans, researchers found consistent evidence that Hybridopa™ was associated with changes in a key brain region involved in controlling movement. Participants who used Hybridopa™ showed less intact brain fibers in this region, stronger communication with other movement-related areas, and more efficient activity across the brain networks that support movement. Importantly, these brain changes were accompanied by meaningful improvements in standard clinical measures of Parkinson’s symptoms. The study also found that the more participants engaged with Remepy’s training program, the greater their clinical improvement, suggesting a strong link between digital therapy, changes in the brain, and better motor function.
This is the first study to show that multiple advanced brain imaging techniques independently identified the same brain changes following a digital therapeutic intervention for Parkinson’s disease. Remarkably, these changes emerged within just a few weeks in a brain region that is known to be affected by Parkinson’s. The findings provide new evidence that targeted digital training may help the brain adapt by strengthening and reorganizing its neural connections, even in the presence of a progressive neurodegenerative disease. The results also support the growing view that digital therapeutics can complement medication by promoting the brain’s natural ability to change and learn, a process known as neuroplasticity.
About Hybridopa™
Hybridopa™, for the treatment of Parkinson’s disease, combines immediate-release levodopa/carbidopa with DopApp™, a therapeutic protocol delivered through a mobile application. Hybridopa™ adapts to patient performance, behavior, and clinical status to enhance both motor and non-motor symptoms in Parkinson’s disease. Currently, Phase III ready, Hybridopa™ is an investigational product and has not yet been approved by the FDA or any regulatory authority.