Trial of Stem Cell-derived Therapy for Parkinson’s to Open in Sweden
Phase 1/2 study of STEM-PD in bringing dopaminergic neurons into brain
A request to launch a first Phase 1/2 clinical trial of a stem cell-based therapy in people with Parkinson’s disease has been approved by the Swedish Medical Products Agency.
The therapy, called STEM-PD, consists of stem cell-derived dopamine-producing, or dopaminergic, neurons that are expected to replace the dopaminergic neurons that are progressively lost in Parkinson’s. Dopamine is a major chemical messenger in the brain.
“We are looking forward to this clinical study of STEM-PD, hoping that it could potentially help reduce the significant burden of Parkinson’s disease,” Malin Parmar, PhD, a professor at Lund University, Sweden, which owns the STEM-PD product, said in a university press release.
Parmar is leading the STEM-PD team in close collaboration with colleagues at Skåne University Hospital, also in Lund, and those at the University of Cambridge, Cambridge University Hospitals, and Imperial College London in the U.K.
“This has been a massive team effort for over a decade, and the regulatory approval is a major and important milestone,” Parmar added.
Trial enrolling 8 people with moderate Parkinson’s by invitation
Skåne University is the trial’s clinical sponsor, and all eight enrolled patients will undergo treatment there. The trial is expected to open once a clinical site inspection is given by authorities in Sweden.
Eight adults with moderate symptoms of Parkinson’s will be recruited by invitation, with invitations first sent to potentially eligible patients in Sweden and then possibly being extended to those being seen at Cambridge University Hospitals. It is not possible to volunteer to participate in this study.
Parkinson’s is characterized by the progressive loss of dopaminergic neurons in the substantia nigra region of the brain. Many of these neurons send signals to the striatum, a brain region involved in voluntary movement control.
When this fails to happen, Parkinson’s motor symptoms result, usually beginning as tremor, slowness of movement, and difficulty walking and balancing.
Current disease therapies focus mainly on restoring dopamine signaling in the brain to reduce symptom severity. But research efforts are increasingly focused on cell-based therapy to replace lost dopaminergic neurons — tackling the neurodegenerative disorder’s underlying cause.
The STEM-PD product is derived from human stem cells of embryos that can mature into almost any type of cell in the body.
“The use of stem cells will in theory enable us to make unlimited amounts of [dopaminergic] neurons and thus opens the prospect of producing this therapy to a wide patient population. This could transform the way we treat Parkinson’s disease,” said Roger Barker, PhD, the study’s clinical lead and principal investigator. Barker is a professor of clinical neuroscience at the University of Cambridge.
The stem cells were reprogrammed in the lab to mature into dopamine-producing neurons that can be transplanted into the striatum of people with Parkinson’s. The STEM-PD product was manufactured at the Royal Free Hospital in London under good manufacturing practice guidelines to ensure that the cells are safe and consistent between batches, the release stated.
The move into clinical testing is supported by preclinical studies in animal models of Parkinson’s where the dopaminergic neurons were shown to safely restore lost motor function.
“The STEM-PD product is safe and highly efficacious in reverting motor deficits in preclinical models of Parkinson’s disease,” said Agnete Kirkeby, PhD, an associate professor at Lund University who led the therapy’s early development.
Safety of stem cell-based Parkinson’s therapy at varying doses among goals
The STEM-PD trial, identified in the release as EudraCT 2021-001366-38, will test increasing doses of the therapy in eight Parkinson’s patients.
Participants will have the dopamine-producing neurons transplanted directly into their striatum by stereotactic surgery using a custom-built device. Stereotactic surgery uses a system of coordinates that allows a neurosurgeon to precisely map the transplant into the striatum.
Skåne University Hospital has a history of similar cell transplant work.
“Our teams have previously performed cell transplantation trials in Parkinson’s disease, but this is the first trial using a stem cell derived medicinal product for replacement of dopamine neurons,” said Håkan Widner, sponsor representative from Skåne University Hospital, where he works as a senior consultant in neurology.
The trial’s main goal is to determine the safety and tolerability of the transplanted dopamine-making neurons one year after the procedure. As secondary goals, the researchers will look at the survival and function of the transplanted cells using brain imaging, as well as changes in symptom severity among treated patients.
Preclinical and clinical studies of STEM-PD have been funded by national and European Union funding agencies. The trial is also being supported by Novo Nordisk, marking the start of a collaboration for future product development.