Training app paired with levodopa eases Parkinson’s symptoms
Hybridopa program leads to changes in brain networks involved in movement
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- Hybridopa, a digital app combined with levodopa, eased Parkinson's motor symptoms.
- This therapy induced structural and functional brain changes, suggesting neuroplasticity.
- It offers an integrated treatment approach for Parkinson's, with a Phase 3 trial planned.
Patients participating in a three-week digital intervention program designed to complement levodopa, the standard treatment for Parkinson’s disease, showed measurable structural and functional changes in brain networks involved in movement, accompanied by meaningful easing of motor symptoms.
The pilot study evaluated Remepy‘s investigational hybrid therapy, Hybridopa, in 32 adults with Parkinson’s disease who had participated in a Phase 2a trial. That study showed that people receiving Hybridopa, which combines levodopa with a prescription digital program called DopApp, experienced greater easing of motor and nonmotor symptoms than those given levodopa along with a placebo app.
The Phase 2a trial also found functional changes in brain networks involved in movement and mood regulation. The new findings add evidence of structural changes in those movement-related brain networks.
Remepy said the results suggest that Hybridopa may promote neuroplasticity — the brain’s ability to reorganize and strengthen its neural connections in response to learning — helping explain the clinical benefits seen in the earlier trial.
“Our Phase IIa trial showed that Hybridopa delivers meaningful clinical improvements for people living with Parkinson’s disease,” Or Shoval, cofounder and co-CEO of Remepy, said in a company press release. “This publication helps explain the neural mechanisms underlying those effects.”
Phase 3 trial planned
“Together, these findings support a shift in Parkinson’s treatment toward integrated approaches that combine pharmacological therapy with structured, system-level digital interventions,” said Michal Tsur, PhD, cofounder and co-CEO of Remepy. “This growing body of clinical and mechanistic evidence … is what motivates us to advance Hybridopa into Phase III later this year.”
The study, “Local and global microstructural and functional thalamomotor connectivity alterations in Parkinson’s disease following motor learning,” was published in npj Parkinson’s Disease.
Parkinson’s is caused by the progressive loss of nerve cells that produce dopamine, a brain chemical essential for controlling movement. In addition to motor symptoms, the disease can also cause nonmotor problems, including cognitive impairment. Although levodopa remains the standard Parkinson’s treatment, some motor symptoms often remain inadequately controlled.
Parkinson’s care often includes nonpharmacological interventions such as physiotherapy, balance and strength training, occupational therapy, and gait exercises. However, many people face barriers to accessing such therapies because of geographic, financial, logistical, or health literacy challenges. Digital health technologies could help bridge that gap by supporting personalized rehabilitation at home.
DopApp guides users through personalized virtual navigation exercises designed to train spatial memory and navigation abilities, which are often impaired in people with Parkinson’s. The exercises gradually reduce visual input, encouraging users to rely on auditory cues and spatial memory to navigate virtual mazes, an approach designed to promote learning-induced neuroplasticity. The app also includes rehabilitation and psychological support modules.
The researchers wanted to investigate whether the digital training used in Hybridopa induced structural and functional brain changes that could help explain the motor improvements observed in the earlier Phase 2a trial.
To do so, they enrolled 32 participants from the previous Phase 2a trial who were receiving stable levodopa treatment. The participants had a mean age of 65.8, 59% were men, and they had been living with Parkinson’s for an average of 5.9 years. Eighteen participants were assigned to use DopApp, while 14 used a placebo app containing educational content.
After completing the three-week program, participants underwent clinical assessments and three complementary brain MRI scans to examine changes in brain structure, communication between movement-related regions, and the organization of motor networks.
Brain scans consistently showed that the intervention altered the structure, communication, and organization of brain networks involved in movement. Participants using DopApp showed signs of microstructural reorganization of nerve fibers in the thalamus, a brain region that relays movement-related signals, and stronger communication between the thalamus and the brain’s primary movement-control region. They also showed greater local efficiency, a measure of how effectively nearby brain regions exchange information, within motor networks.
These brain changes were accompanied by improved motor function and a reduction in motor symptoms, as measured by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III. People who engaged more successfully with the digital training experienced greater easing of motor symptoms, and this relationship was independent of symptom severity at the start of the study. According to Remepy, this suggests a strong link between digital therapy, brain changes, and improved motor function.
“Parkinson’s disease involves more than dopamine deficiency. It reflects dysfunction across distributed brain networks,” said Amir Amedi, PhD, chief science officer at 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.”
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