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Two early-stage clinical trials demonstrate the safety and potential effectiveness of stem cell therapies to treat Parkinson’s disease (PD), the second most common neurological disease worldwide.

PD is characterized by the progressive loss of neurons that produce dopamine. Although current treatments, such as levodopa, can alleviate symptoms in the early stages of PD, their efficacy declines, and they are often accompanied by side effects such as dyskinesia.

Cell-based therapies that replenish dopamine neurons in the brain are showing early promise as a potentially more effective treatment with fewer adverse effects. The two new studies were published online on April 16 in Nature.

‘Significant First Step’

In a phase 2/3 trial conducted in Japan, seven patients with PD underwent bilateral striatal transplantation of dopaminergic precursor cells derived from human induced pluripotent stem (iPS) cells, with immunosuppression, and were monitored for 24 months.

“This trial showed that iPS cell–derived dopaminergic neurons are safe, produce dopamine in the brain, and ameliorate neurological symptoms. I think it is a significant first step,” study investigator Jun Takahashi, MD, PhD, director and professor, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan, told Medscape Medical News.

No serious adverse events were reported during the study period, and the transplanted cells produced dopamine without forming tumors, a serious risk associated with stem cell therapy.

Among the six patients evaluated for efficacy, five showed improvement in the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Part III, while on medication and when they stopped taking it, four continued to show improvement.

The average changes of all six patients were 9.5 points (20.4%) and 4.3 points (35.7%) for the OFF and ON scores, respectively. Hoehn-Yahr stages improved in four patients.

Takahashi noted that cell transplantation can be applied when medication for PD becomes less effective or causes side effects.

“In this sense, cell transplantation therapy is adjunctive. In the future, the best scenario is that cell transplantation alone can replace lost dopaminergic neurons and cure the patient,” Takahashi said.

Encouraging But Preliminary 

In a separate phase 1 clinical trial, also published in Nature, an “off-the-shelf” dopaminergic progenitor cell product (bemdaneprocel) derived from human embryonic stem cells was grafted bilaterally into the putamen of 12 patients with PD from the United States and Canada.

Five patients received a low-dose (0.9 million cells per putamen) and seven received a high-dose (2.7 million cells per putamen), coupled with 1 year of immunosuppression.

The trial achieved its primary objectives of safety and tolerability up to 18 months after transplantation, with no adverse events related to the cell product, reported the investigators led by Viviane Tabar, MD, Memorial Sloan Kettering Cancer Center in New York City.

The transplanted cells survived, became engrafted and produced dopamine, with no evidence of graft-induced dyskinesias.

Secondary and exploratory clinical outcomes showed improvement or stability, including improvement in the MDS-UPDRS, Part III, OFF scores by an average of 23 points in the high-dose cohort, reflecting improved motor function without PD medication.

The author of a Nature News and Views said these results are “encouraging” because they show that the use of allogeneic transplants for treatment of PD is likely to be safe.

“To confirm their effectiveness, however, more research is needed. These two trials were small, open-label studies in which both the investigators and the participants were aware of who received what treatment,” wrote Hideyuki Okano, MD, PhD, with the Keio University Regenerative Medicine Research Center, Kawasaki, Japan.

“Because of this, there is a possibility that the results on efficacy were influenced by the placebo effect or investigator bias. Nevertheless, the fact that both independent trials proved to be safe, and hinted at possible efficacy, is an important step towards the establishment of this cell therapy for Parkinson’s disease in wider society. The next stages of clinical trials, phases 2 and 3, are awaited to fully assess the efficacy of these interventions,” Okano concluded.

Beware of Scams

Commenting on this research for Medscape Medical News, Michael S. Okun, MD, medical advisor, Parkinson’s Foundation, and director of the Normal Fixel Institute for Neurological Diseases, University of Florida Health, Gainesville, noted that, over the past two plus decades, stem cells have generated “tremendous interest, excitement and hope for Parkinson’s disease. These two most recent studies are small but promising.”

Okun cautioned that it’s tough to judge short- and long-term outcomes because each of the two studies included so few subjects. “The safety of each approach was reassuring, and one very important finding was the absence of runaway dyskinesia, which was a ‘showstopper’ for previous Parkinson’s stem cell trials,” Okun said.

Okun also said its important for patients and families to be wary of what has been referred to as “stem cell tourism.”

These two newly published studies are both “legitimate,” he told Medscape Medical News.

“We are however aware of thousands of clinics around the world offering a stem cell ‘cure for cash’ deal. We are also aware of serious complications resulting from stem cell therapies.”

“We recommend never paying for an unproven experimental treatment. We also recommend that before saying yes to anyone approaching you with cash for a stem cell treatment you request copies of two critical documents: The Institutional Review Board approval to conduct research on you as a human subject, and also the informed consent form. Bring the documents to your doctor and healthcare team for discussion and shared decision-making,” said Okun.

The study by Takahashi and colleagues was supported by a grant from the Research Project for Practical Application of Regenerative Medicine of the Japan Agency for Medical Research and Development. The study by Tabar and colleagues was sponsored by BlueRock Therapeutics. Disclosures for study authors and News and Views author are available with the original articles. Okun had no relevant disclosures.