Early Data Indicate Cell Therapies Could ‘Reset the Clock’ in Parkinson’s

 Could stem cell therapies make the Parkinsonian brain generate dopamine again? Some companies, including BlueRock Therapeutics and International Stem Cell Corporation, are banking on it.

Parkinson’s disease is currently treated with dopamine replacement agents, but the efficacy of these drugs is limited and they come with challenging side effects. Some in the stem cell field say these new therapies, though early-stage, could ultimately be a better, safer option.

In a March 2024 report, GlobalData touted the “early promise” of cell therapies to address the motor and non-motor symptoms of Parkinson’s disease with minimal adverse effects.

‘Resetting the Clock’

With more than 10 million people around the world living with Parkinson’s disease, the treatment market is currently valued at $5.56 billion and is expected to reach $6.63 billion by 2029.

A progressive disease of the nervous system, Parkinson’s is characterized by the degradation of neurons in the part of the brain that controls movement. The loss of these neurons slows the production of dopamine, leading to a combination of motor symptoms, including writhing movements, resting tremors and muscle stiffness, which can be lessened with levodopa and dopamine-agonists—drugs that behave like dopamine. The disease also brings non-motor symptoms, including depression, hyposmia, dysphasia and psychosis.

Levodopa is currently the “gold standard” treatment for Parkinson’s. Although it provides a dopamine kick, the drug is laden with severe adverse effects, including hallucinations, dyskinesia and loss of impulse control. These side effects can occur a dopamine response is stimulated in several parts of the brain through medication, Agnete Kirkeby, a stem cell scientist at Lund University and the University of Copenhagen, told BioSpace. Levodopa also provides only a small window of relief for patients, Kirkeby said.

In an emailed statement to BioSpace, GlobalData analysts Lorraine Palmer and Christie Wong said early clinical trials of stem cell transplantation in Parkinson’s have shown a reduction in motor and non-motor symptoms. “However, the subject size of these clinical trials have been small and were not powered to measure statistical significance,” they said, adding that large-scale, pivotal trials will be required to investigate how safely and how well the therapies work.

“Currently, there are no therapies which recover lost dopaminergic neurons so if cell therapies do end up meeting their hopes of replacing dopaminergic neurons,” they could be market changers, Palmer and Wong said.

During her postdoctoral days at Lund, Kirkeby, along with her supervisor, designed a method to grow transplantable dopamine cells from embryonic stem cells. “When we transplant the cells, we transplant [them] to a very particular region of the brain that is involved in motor control,” she explained. Kirkeby is currently leading a preclinical study of STEM-PD sponsored by Lund, a stem-cell therapy intended to replace lost dopamine neurons in the brains of Parkinson’s patients.

Cambridge, Mass.–based BlueRock Therapeutics, a Bayer subsidiary, is also developing a stem cell–based therapy, called bemdaneprocel. “You can think about it almost like you’re resetting the clock for those people who live with Parkinson’s disease by providing them cells, which have the potential to integrate and re-establish some of the neural networks and circuitry in that part of the brain,” Ahmed Enayetallah, head of development at BlueRock, told BioSpace.

Cell Therapies for Parkinson’s in the Pipeline

There are currently seven stem cell therapies for Parkinson’s disease in Phase I clinical trials or later. Three of these—sponsored by BlueRock, Celavie Biosciences and International Stem Cell Corporation—have completed and published results.

In the Phase I trial of bemdaneprocel, neuronal progenitor stem cells derived from donors were transplanted into 12 patients, whose progress was monitored for 18 months. During the first year, the patients were treated with immunosuppressive drugs. The cells survived and bemdaneprocel was tolerated by patients throughout the trial period, Enayetallah said, even after immunosuppression was discontinued.

The trial met multiple clinical endpoints and broadened the window at which the patients experienced relief from disease symptoms, he added. Unlike with current treatments, Enayetallah said, there were no reported cases of dyskinesia or other adverse events except gastrointestinal bleeding and seizure, which he attributed to the surgical procedure and not the therapy itself.

Having a one-time treatment for Parkinson’s disease would be a paradigm shift, Enayetallah said.

Another therapy, ISC-hpNSC, is in development by California-based International Stem Cell Corporation. Upon completion of a Phase I trial, patients’ ON-Time—a period where Parkinson’s medications like levodopa bring about good motor control—increased by 65% over two years, and OFF-Time decreased by 55% within the same period, the company reported in June 2021. The cells were well-tolerated with no serious adverse events.

With therapies such as these, Kirkeby said it is possible that the cells could overgrow and generate too many cells in the brain, but so far, neither trials of STEM-PD nor bemdaneprocel have recorded this adverse effect.

And while stem cell therapies are currently aimed at relieving the motor symptoms of Parkinson’s, Enayetallah said bemdaneprocel’s trial results hint at improved quality of life and psychiatric outcomes. Kirkeby also indicated that her lab is working on stem cell therapies that would target non-motor symptoms such as cognitive impairment.

Enayetallah noted that therapeutic development in Parkinson’s is “incredibly challenging” and plagued with the highest failure rates in drug development. However, he said, the results of BlueRock’s Phase I trial are a significant step toward bringing a “transformational therapy” to patients.

“Cell therapy in neurology is something that hasn’t been explored to that extent before. We’re paving the road here.”

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