Phase 1 Clinical Trial Launched Examines Safety, Efficacy of Stem Cell Treatment for Parkinson Disease

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A first-of-its-kind phase 1 open-label clinical trial at Mass General Brigham is evaluating an innovative treatment for Parkinson disease by using a patient’s own reprogrammed stem cells to replace dopamine neurons damaged by the disease. The treatment aims to address the underlying neuronal loss and restore dopamine function. The new study has already enrolled and treated 3 participants at Brigham and Women’s Hospital.¹

“It is extraordinary to witness that investigators at our institution can bring new treatments to patients through the entire process of laboratory ‘bench to bedside,’ and it inspires many investigators to similarly pursue their scientific and medical insights to reach patients in need,” said Kerry Ressler, MD, PhD, chief scientific officer at McLean Hospital.¹

This phase 1 study is the first trial to test blood-derived autologous iPSC-derived dopamine neurons in patients with Parkinson disease. The trial will include a total of 6 participants and is set to track their progress for at least 12 months to assess the safety and potential benefits of the procedure. It is funded by the National Institute of Health’s National Institute of Neurological Disorders and Stroke.

Developed at McLean Hospital’s Neuroregeneration Research Institute (NRI), the treatment utilizes induced pluripotent stem cells (iPSC) derived from a patient’s blood that are reprogrammed into midbrain dopaminergic neurons, which degenerate in Parkinson disease.¹ By using the patient’s own cells, the approach eliminates immune rejection.¹

The US Food and Drug Administration granted Investigational New Drug approval for the phase 1 trial on August 23, 2023, and the first patient was treated on September 9, 2024. If successful, researchers plan to expand the study into a phase 2A trial to recruit additional participants.

“Seeing this patient-specific dopamine neuron replacement therapy progress from basic research to clinical application is incredibly gratifying,” said Ole Isacson, MD, the founding director of the NRI. “We believe this approach may open up a new treatment paradigm and lead to the development of many additional cell therapies to restore damaged brain systems and replace degenerated brain cells in other diseases.”

This research was built off of decades of work done by Isacson, though he is not directly involved in the trial due to being the innovator patent holder of the technology and a cofounder of Oryon Cell Therapies. In 2015, Isacson contributed to the first study providing evidence of the safety and efficacy of autologous stem cell therapy in a nonhuman primate model. The most successful model from the study found that unilateral engraftment of a cynomolgus monkey iPSCs could provide a gradual onset of functional motor improvement and increased motor activity without a need for immunosuppression.²

A 2020 study from a team, including Isacson, examined the advantages of autologous cell therapy for patients with Parkinson disease. Osborn et al wrote that “When new midbrain dopamine (mDA) neurons… are engrafted into the normal target regions of nigrostriatal dopamine (DA) neurons, they establish synapses with mature host striatal neurons and provide physiologically appropriate DA release and synaptic feedback control in the host brain.”³ The authors concluded that the replacement of DA terminals in this manner may be more effective in bettering the motor symptoms in Parkinson disease. Osborn et al also found that long term benefits to patients with Parkinson disease following fetal DA neuron transplantation have been reported for over 18 years and can prevent progressive worsening of motor scores over at least 14 years.³

References

1. Clinical trial tests novel stem-cell treatment for Parkinson’s disease. News release. March 6, 2025. Accessed March 10, 2025. https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/clinical-trial-novel-stem-cell-treatment-for-parkinsons

2. Hallett PJ, Deleidi M, Astradsson A, et al. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease. Cell Stem Cell. 2015;16(3):269-274.

3. Osborn TM, Hallett PJ, Schumacher JM, et al. Advantages and recent developments of autologous cell therapy for Parkinson's disease patients. Front Cell Neurosci. 2020;14:58.