A landmark study led from Lund, Sweden, has shown that transplanting stem-cell derived dopamine progenitor cells into the brain is feasible. Eight patients were transplanted in the first clinical trial, and no serious side effects directly linked to the transplanted cells were seen during the first year of follow up. The results are published in Nature Medicine.
In Parkinson's disease, patients lose nerve cells in the brain that produce dopamine which leads to symptoms such as slowness of movement, stiffness, gait disturbance and tremor. The current treatments are medications that replace the lost dopamine, but over time these medications often become less effective and cause side effects.
Reaching this primary endpoint and being able to show that the cell product is safe is a great achievement
The therapy tested in the current trial aims to replace the cells that produce dopamine through transplantation of a stem cell-based dopamine nerve cell product to the brain, and the goal is that after being transplanted, they will mature into new dopamine-producing nerve cells in the brain.
"The possibility of replacing dopamine neurons that are lost in Parkinson's disease has been a long-standing goal in the field," said Malin Parmar, Professor of Cellular Neuroscience at Lund University, Sweden, and lead of the STEM-PD program. "The findings represent an important milestone for regenerative medicine approaches in Parkinson's disease and support continued clinical development of stem cell-based therapies."
Eight individuals with Parkinson's disease received the transplanted cell product at two different doses, followed by 12 months of immunosuppression to prevent graft rejection. Seven participants completed 12-month follow-up; one participant died from a pulmonary infection that was not directly related to the cell product. The surgical procedure was generally well tolerated and no graft-induced involuntary movements were observed in the transplanted participants. Clinically, patients remained stable. Imaging using dopamine PET scans provided early indications of graft survival at both 6 and 12 months post-transplantation. Six of the seven participants substantially reduced their dopaminergic medication, a result that will be evaluated over time.
"This represents an exciting new departure on repairing the brain of individuals with Parkinson's using dopamine cells- an approach pioneered in Lund some 40 years ago using fetal dopamine cells. The STEM-PD trial harnessing the expertise of scientists and clinicians from Lund and Cambridge has enabled us to undertake and deliver on one of the first ever stem cell-derived dopamine cell therapies for patients with Parkinson's and we hope this will be the beginning of an exciting new programme that may ultimately benefit the wider Parkinson's community," says Roger Barker, Professor of Clinical Neuroscience at the University of Cambridge, clinical lead of STEM-PD and clinical PI at the UK site.
The STEM-PD research team will now continue the long-term follow-up of the participants to further evaluate safety, graft function, and clinical benefit.
"Reaching this primary endpoint and being able to show that the cell product is safe is a great achievement for this trial, our team, the participating patients but also for all patients suffering from Parkinson's disease. We are hopeful that the early signs of cell survival and clinical improvement we observe will continue to increase over the time and excited to continue the development of this cell therapy," says Gesine Paul-Visse, Professor in Neuropsychiatric Research and Lead PI at Skåne University Hospital, the Swedish clinical site where all patients were treated.
Decades of research at Lund University
STEM-PD builds on decades of research in dopamine cell replacement therapy for Parkinson's Disease at Lund University and pioneering work in translation of pluripotent stem cell technology from experimental studies into clinical evaluation. The therapy consists of dopaminergic neuron progenitors derived from human embryonic stem cells that mature into dopamine-producing neurons following transplantation into the brain. The STEM-PD trial is the first pluripotent stem cell trial approved in Sweden and the first for Parkinson's Disease in Europe.
"The initiation and execution of this clinical trial have only been possible through close collaboration between scientists, clinicians, GMP manufacturing teams, regulatory experts and, most importantly, the participating patients," concludes Malin Parmar.
Publication:
Link to the article in Nature Medicine:
About STEM-PD
STEM-PD is an academic European clinical translation initiative, focused on developing stem cell-based therapies for Parkinson's disease. The program is lead from Lund University with partners from Skåne University Hospital, Cambridge University Hospital, and University College London and combines expertise in stem cell biology, GMP manufacturing, neurosurgery, clinical neurology and regenerative medicine to advance pluripotent stem cell-derived dopamine neuron therapies toward clinical application.
Key facts: research leaders STEM-PD
Malin Parmar, Project lead - Professor, Lund University
Gesine Paul-Visse, Principal Investigator - Professor, Lund University and Senior Consultant Neurologist, Skåne University Hospital in Lund
Roger Barker, Clinical Lead & Principal Investigator - Professor, University of Cambridge and Honorary Consultant Neurologist, Cambridge University Hospitals NHS Foundation Trust
Håkan Widner, Sponsor representative/co-investigator - Associate Professor, Lund University and Senior Consultant Neurologist, Skåne University Hospital in Lund
Hjálmar Bjartmarz, Co-Investigator - Senior Consultant Neurosurgeon, Skåne University Hospital in Lund
Agnete Kirkeby, Pre-clinical development lead at Lund University - today Associate Professor, University of Copenhagen
Paola Piccini, Brain imaging expert - Professor and Honorary Consultant, Imperial College London
Oskar Hansson, PET imaging - Professor at Lund University
Ruben Smith, PET imaging - Associate Professor and researcher at Lund University and Physician at Skåne University Hospital
The clinical trial is managed by Cambridge Clinical trials unit Neuroscience theme and Skane University Hospital neurology research unit. Cellular Intelligence will lead the next phase of clinical development, advancing the STEM-PD program toward a planned Phase II trial.
