Phase 1 trial of cell therapy seeks more Parkinson’s patients
Approach uses stem cells from blood cells to replace dopaminergic neurons
A small Phase 1 clinical trial testing a treatment approach that uses stem cells derived from a patient’s blood cells to replace the dopamine-producing neurons progressively lost in Parkinson’s disease is looking for three more patients.
The first-of-its-kind Phase 1 study (NCT06422208), being conducted at Harvard Medical School’s Brigham and Women’s Hospital, has already enrolled and treated three of the six Parkinson’s patients it seeks to include. Eligible participants, ages 55 to 80, must have a diagnosis of Parkinson’s for at least five years and show a response to dopaminergic medications, which are those that increase or mimic dopamine, a major brain signaling molecule involved in motor control.
“Seeing this transformational new patient cell-based replacement of their own [dopamine-producing] neurons come to fruition — from the very basic science breakthroughs in our lab to be completely translated into a clinical application for patients suffering from Parkinson’s disease — is very gratifying,” Ole Isacson, a professor at Mass General Brigham and the researcher at McLean Hospital’s Neuroregeneration Research Institute (NRI) who led the preclinical research that laid the trial’s foundation, said in a Mass General Brigham press release. “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.”
Isacson isn’t involved in this trial, but is the innovator patent holder of the cell therapy technology and a cofounder of Oryon Cell Therapies, which has the license to the technology.
A hallmark of Parkinson’s is the gradual loss of dopaminergic neurons, the nerve cells in the brain responsible for producing dopamine. Deficient levels of dopamine disrupt nerve signaling in the brain and lead to the motor symptoms that mark the disease.
Stem cells, which can give rise to all types of cells when exposed to the right molecular cues, could be used to restore the pool of dopaminergic neurons in Parkinson’s. Once in the brain, stem cell-derived dopaminergic neurons would provide a new source of dopamine, easing motor symptoms and slowing the disease’s progression.
A patient-derived cell therapy
Isacson led pioneering work at NRI that showed stem cells can turn into working dopaminergic neurons when transplanted into an affected brain region of a rat model of Parkinson’s and that patient-derived stem cells can be used for this purpose.
The patient-derived approach is based on induced pluripotent stem cells (iPSCs), a type of stem cell generated from fully mature cells, like skin or blood cells, that are programmed back to a stem cell-like state, where they can give rise to almost every type of human cell.
In the ongoing Phase 1 trial, blood cells from each participant are collected and reprogrammed into iPSCs. They are then grown in the lab in the presence of specific molecular cues that promote their maturation into dopaminergic neurons. The specialized neurons, which can be frozen until use, are then injected during a single surgical session into one side of the putamen, a region of the brain that controls movement and is affected in Parkinson’s and other neurodegenerative diseases.
Using the patient’s own cells — called an autologous approach — avoids needing immunosuppressive medications to thwart immune reactions against transplanted cells from donors.
The trial’s main goal is to check how safe this approach is by recording adverse events at 12 and 18 months after the surgery. Secondary goals include assessing score changes in the MDS Unified Parkinson’s Disease Rating Scale- Parts II and III, which measure the severity of motor symptoms and their impact on daily living, over 18 months.
The researchers will also measure changes in clinical measures of dyskinesia (uncontrolled movements) and cognitive function, along with on time without troublesome dyskinesia and off time, based on diary entries. On time refers to periods when motor symptoms are controlled, while off periods are when motor symptom worsen due to the effects of medication wearing off.
If results are positive, the researchers hope to launch a Phase 2a trial to test the therapy in a larger number of patients.
“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, the chief scientific officer at McLean Hospital.
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