The hallmark motor symptoms of Parkinson's disease — such as involuntary movements, which are called dyskinesia, and rigidity and tremors — are the result of a progressive loss of dopamine-producing neurons in a part of the brain called the basal ganglia.
For most patients with Parkinson's, managing these symptoms requires long-term treatment with levodopa — a drug that replaces dopamine in the brain — or surgical options such as deep-brain stimulation.
Unfortunately, these treatment options present numerous challenges. As the disease progresses and more dopamine-producing neurons are lost, existing treatments become increasingly less effective at managing motor symptoms.
Even in earlier stages, symptom control remains imperfect, with many patients experiencing periods known as "off" times — when motor symptoms return despite medication.
A recent Phase 1 clinical trial is laying the foundation for a revolutionary new treatment option — bemdaneprocel, an injectable treatment made from stem cells. These cells develop into dopamine-producing neurons, once inside the brain.
Unlike current treatments, bemdaneprocel aims to target the root cause of Parkinson's motor symptoms by replacing lost neurons. The team, which included researchers from UHN's Krembil Research Institute (Krembil) — Drs. Alfonso Fasano, Andres Lozano and Suneil Kalia — studied whether injecting bemdaneprocel into the basal ganglia of Parkinson's patients is safe.
Dr. Lozano, the lead investigator on this study at UHN, is a Senior Scientist at Krembil Research Institute; Dr. Fasano, a co-investigator on the study, is a clinician investigator at the UHN's Krembil Brain Institute and an affiliate scientist at UHN's KITE Research Institute; Dr. Kalia, also a co-investigator on the study, is a Senior Scientist with Krembil Research Institute and KITE. All three are professors in the Temerty Faculty of Medicine at the University of Toronto.
The trial results were promising. The treatment was well tolerated, with no off-target effects such as graft-induced dyskinesias — new dyskinesias brought on by the injected cells — observed during the 18-month follow-up period.
The trial also showed that the newly developed dopamine-producing neurons remained alive 18 months post-injection.
Even more importantly, the team saw clinically significant improvements in participants' motor symptoms — including reduced "off" times.
The improvements were also found to be dose-dependent, as patients in the high-dose cohort showed greater improvements than those in the low-dose cohort.
Although it is unclear whether these improvements were directly caused by bemdaneprocel treatment — as participants continued taking levodopa throughout the course of this trial — these initial findings offer hope for patients with Parkinson's disease.
Despite its small size and focus on safety, the trial's results suggest real potential for bemdaneprocel as a future treatment. The most recent post-study follow-up, at 24-months after treatment, adds further support.
Larger, longer trials will help confirm the therapy's safety and determine if these early improvements can be replicated.
This early success brings us closer to a future where people with Parkinson's have access to therapies that restore function, not just manage symptoms.
This work was supported by BlueRock Therapeutics and UHN Foundation.
The first author on this study is Dr. Viviane Tabar, a neurosurgeon at the Memorial Sloan Kettering Cancer Center. The senior authors on this study are Drs. Lorenz Studer and Claire Henchcliffe. Dr. Studer is the Director of the Center for Stem Cell Biology at the Memorial Sloan Kettering Cancer Center. Dr. Henchcliffe is the Chair and Stanley van den Noort Professor of Neurology at the University of California Irvine School of Medicine.
BlueRock Therapeutics was founded in 2016 at UHN by Drs. Gordon Keller and Michael Laflamme. In 2019, BlueRock Therapeutics was fully acquired by Bayer AG.
For a full list of competing interests, see the publication.
