Funding from The Parkinson Alliance helped to finance the following Parkinson’s research. Grantees were selected by scientific review committees of participating organizations. Updates will be posted, when available.
Project Title: ABBV-951 Subcutaneous Carbidopa/Levodopa Infusion Study
Principal Investigator(s): Dr. Jill Farmer, Global Neuroscience Institute
Objective/Rationale: To see if a continuous delivery of a liquid formulation of carbidopa/levodopa just under the skin can provide the same clinical effectiveness as oral carbidopa/levodopa and potentially improve symptomatic ON time and reduce OFF periods since the medication will be infused continuously over 24 hours.
Project Description/Methods/Design: This is a double blind, randomized, placebo control study – so patients will either be taking oral carbidopa/levodopa IR and receiving placebo through the pump OR they will be getting medication through the pump and taking placebo oral medication. Neither the patient in the study, nor the doctor will know if they are getting placebo or real medication when they conduct their evaluation.
Relevance to Treatment of Parkinson’s Disease: Relevance to the treatment of Parkinson’s disease is profound. Our current goal of medication is to mimic a steady state of dopamine and right now the only way we can do this is to dose multiple medications multiple times a day. This will deliver a steady state continuously, avoid medication wearing off, and in theory keep patients ON more consistently.
Expected Outcome: The expected outcome is that this will be a well-tolerated device with good clinical efficacy.
September 2021 Project Update:
This is a study to look at the continuous delivery of a liquid form of carbidopa/levodopa through a small port just under the skin. Three participants were screened in the Abbvie M15-736 study. Of these two enrolled, were randomized and completed the double-blind portion of the study. While we are still blinded to their treatment condition, both patients rolled over into open label. Open label study activities are ongoing and those receiving treatment are doing well. While there are challenges to the subcutaneous route such as size of pump and selection of site to infuse, this delivery system is very promising. This is important because one of the biggest frustrations to patients and doctors is managing fluctuating symptoms as the disease progresses and the medication is not as consistent in keeping the symptoms from returning – i.e., the medication wears off more. If there was a way to have the medication delivered continuously then the frequency of wearing off would conceivably be less, and this could improve patients’ symptoms and ultimately their quality of life.
Project Title: Vibrotactile Coordinated Reset as a Non-Invasive Therapy to Treat Parkinson’s Disease
Investigator/Author: Peter Tass
Objective: Parkinson’s disease (PD) is often associated with motor symptoms such as stiffness, poor balance and trembling. Parkinson’s patients typically also suffer from impairments of sensory information processing, including a compromised sense of touch, as well as impairments of the integration of sensory information and motor commands, all of which are required for normal movement. Although pharmacological therapy and Deep Brain Stimulation (DBS) may provide fundamental relief for Parkinson’s patients, both therapy options may not be sufficiently effective and may cause side effects. DBS is also an invasive procedure and hence not without risk. We have developed an alternative, completely non-invasive treatment approach called vibrotacile Coordinated Reset (vCR) simulation. This procedure applies vibrotactile stimuli to the fingertips of patients through convenient gloves for a few hours regularly or occasionally. These stimuli help to remodel abnormal brain connections and may lead to long-lasting functional recovery. In a phase I study and two case series studies we have demonstrated that vCR therapy is safe and tolerable. These studies also showed that the therapeutic effects last over a long period of time, can accumulate with further use, and may also lead to a decrease in the amount of medication required. These studies helped us to improve vCR stimulus parameters and assess effect size required for a proof-of-concept study. An example video of a patient following vCR therapy may be found at https://www.youtube.com/watch?v=bMVC5IcNxIM.
Methods/Design: We will perform a 7-month double-blind placebo-controlled proof-of-concept study. A minimum of 30 PD patients will be included. Patients will be randomly placed into a real (n = 15) or sham (n = 15) vCR condition. Patients will receive a maximum of 4 hours of daily real vCR or sham vCR at home for 6-months. To measure long term effects, patients will receive no stimulation for 1 month after the 6-month follow-up appointment. Clinically established motor and quality of life assessments will be measured off medication at baseline, 3-months, 6-months, and after a 1-month pause in stimulation at 7-months.
Relevance to Diagnosis/Treatment of Parkinson’s Disease: We hope to establish a novel, non-invasive treatment option which provides significant acute and long-term relief of Parkinson’s symptoms by remodeling abnormal plasticity (brain connections) in Parkinson’s-related brain circuits in a sustained way by convenient vibrotacile fingertip stimulation.
Expected Outcome: We expect our research to rigorously establish that vCR therapy provides an effective non-invasive treatment which causes sustained relief for PD patients by improving gait and balance and reducing characteristic Parkinson’s symptoms, like tremor. This therapy may give hope to individuals who do not respond well to medication or are seeking a non-invasive therapy that can reduce reliance on medication. In addition, we expect our study to reveal optimal vCR dosage patterns.
May 2021 Project Update:
Clinically, in these studies, we observed significantly improved motor ability. EEG recordings observed from study 1 indicated a significant decrease in off-medication cortical sensorimotor high beta power (21 – 30 Hz) at rest after 3 months of daily noisy vCR therapy. Computationally, vCR and noisy vCR cause comparable parameter-robust long-lasting synaptic decoupling and neuronal desynchronization. In these feasibility studies of eight PD patients, regular vCR and noisy vCR were well tolerated, produced no side effects, and delivered sustained cumulative improvement of motor performance, which is congruent with our computational findings. In study 1, reduction of high beta band power over the sensorimotor cortex may suggest noisy vCR is effectively modulating the beta band at the cortical level, which may play a role in improved motor ability. These encouraging therapeutic results enable us to properly plan a proof-of-concept study.