Learn the Latest on Stem Cell Therapy for Treating Parkinson’s
Parkinson’s disease (PD) is characterized by a loss of neurons in the brain that communicate using the chemical dopamine. The mainstay of treatment is to restore this communication, using medications that increase the levels of dopamine in the brain. But what if instead, PD could be treated not by giving dopamine but by restoring the lost neurons? This is the idea behind cell-based therapies for Parkinson’s disease that entail implanting stem cells into the brain to take the place of the cells that have been lost. If research succeeds in designing a cell-based therapy that could replace the cells lost in the disease, the treatment of PD could be transformed.
Are stem cells an effective treatment for Parkinson’s disease?
There is no FDA approved stem cell therapy for Parkinson’s disease. However, recent clinical trials have been promising, and researchers have been trying to develop this type of treatment for decades. There are two crucial steps to this process: Harvesting stem cells—cells with the potential to develop into many different types of cells in the body—and then coaxing those stem cells into becoming nerve cells that produce dopamine.
Current research is focused on deciphering the best source of stem cells to use, the best ways to turn the stem cells into dopaminergic neurons and the best ways to introduce the cells into the brain for maximal effect and minimal harm. In the last few years, there has been more momentum forward, bringing new hope to the field of cell-based therapies for PD.
The ideal goal is to create treatments utilizing stem cells to take the place of the neurons lost in PD. The hope is that this would not only alleviate symptoms of PD but could potentially repair damage to the brain that PD causes, thereby slowing the progression of the disease.
What types of stem cells can be considered for cell-based Parkinson’s treatments?
1. Embryonic stem cells (ESCs) – Stem cells derived from a human embryo, typically at a very early developmental stage. Early embryos created by in vitro fertilization (IVF) and are not going to be used for pregnancy are typically the source of these cells. (This is as opposed to fetal stem cells which are typically derived from an older embryo.)
2. Adult derived stem cells (also called tissue-specific stem cells) – Stem cells found among, and then isolated from, differentiated cells in an adult. The most well understood of these are hematopoietic stem cells found in adult blood and bone marrow, which have been used clinically for decades, mostly to treat blood cancers and other disorders of the blood and immune systems.
3. Umbilical cord stem cells – Hematopoietic stem cells are also found in umbilical cord blood retrieved after delivery. These too are used clinically to treat blood cancers and some rare genetic disorders.
4. Mesenchymal stem cells — Also known as stromal cells, these stem cells are present in many tissues such as bone, cartilage and fat. They remain poorly understood, but likely have regenerative potential.
5. Induced pluripotent stem cells (iPSCs) – Stem cells created from adult skin or blood cells that have been reprogrammed to revert to an embryonic state.
6. Human parthenogenetic stem cells – Stem cells created from an unfertilized human ovum.
Clinical trials of stem cell treatments for Parkinson’s disease
The only way to bring legitimate, scientifically proven and approved stem cell treatments to the PD community is through clinical trials. If you are interested in pursuing a stem cell treatment for PD, it is strongly advised to enroll in a clinical trial at an academic medical institution rather than a commercial clinic (more on this below). You may be able to get early access to stem cell treatments while also helping bring such treatments to fruition for the larger PD community.
It is incredibly important to note however, that clinical trials that are entered on clinicaltrials.gov, the NIH-managed directory of all clinical trials, are not vetted by the NIH, and commercial stem cell clinics can put their treatments on this site. Most people don’t realize this, which led clinicaltrials.gov to put a disclaimer on their site stating: “The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.”
Therefore, in order to use clinicaltrials.gov safely, focus on the trials conducted at academic medical centers in the United States, not commercial clinics.
Recent and current clinical trials for stem cell treatments
Phase I study using Bemdaneprocel stem cells in the brain
A recently-completed phase I study investigated the surgical transplantation of stem cells called Bemdaneprocel (BRT-DA01, previously known as MSK-DA01) into an area of the brain called the putamen. These cells are dopamine neuron precursors that are derived from embryonic stem cells. People in the trial took medication to partially suppress their immune system (aimed to prevent the body from rejecting the cells). End points of the study included safety, tolerability, evidence of cell survival (using MRI and PET scans of the brain), as well as the effect on PD symptoms. Twelve people with PD were included in this open-label study (a study that does not have a control group). The study demonstrated that the treatment was safe and well-tolerated. Transplantation of the cells was feasible and resulted in successful cell survival and engraftment. A phase II study is currently being planned. The people who received the transplanted cells in the original study are continuing to be studied over the course of a second year.
Phase IIA studying using mesenchymal stem cells to treat Parkinson’s
A recently completed phase IIA study, investigated the intravenous infusion of bone marrow derived mesenchymal stem cells as a disease-modifying therapy for PD. The goal of this study was to select the safest and most effective number of repeat doses of infusions. The study was double-blind and randomized. There were three treatment arms, studying a total of 45 people with PD. This study was a follow up to one published in 2021, which was a phase I study of 20 people with mild/moderate PD who were each assigned to a single intravenous infusion of one of four doses of bone marrow-derived mesenchymal stem cells, with evaluations over the course of the year. The study demonstrated that the treatment was safe and well tolerated. Treatment was correlated to a reduction in the OFF state on the United Parkinson Disease Rating Scale, with the highest dose correlated to the most significant effect.
Studies recruiting participants for iPSC treatment
A phase I/IIa study is currently recruiting nine participants with PD to test the safety and tolerability of injecting ANPD001 cells, iPSCs that mature into dopamine-producing cells, into the putamen of participants with PD. All participants will have iPSCs manufactured from their own skin biopsies, thereby eliminating the need to take an immunosuppressant medication. The effect on PD symptoms, safety and tolerability, and cell survival will be assessed using MRI and PET imaging scans of the brain for five years after implantation. Safety and tolerability will be assessed annually for an additional 10 years via telephone call.
Another study is about to start recruiting with a goal of six people with PD. The study will similarly evaluate the surgical transplantation of dopamine neurons derived from induced pluripotent stem cells (iPSCs), into the putamen. These iPSCs will be made from blood cells of people with PD and then surgically transplanted into the same person, which again, eliminates the need to take an immunosuppressant medication. The trial will assess the safety of the injected cells and will also measure the effects of the transplanted autologous dopamine neurons on PD symptoms.
Phase I study using embryonic stem cells
Another phase I study is underway investigating STEM-PD cells, dopamine precursor cells derived from embryonic stem cells (generated by a different research facility than Bemdaneprocel) and their transplantation into the putamen of eight people with PD.
Does APDA fund any stem cell research?
APDA is funding numerous research projects using iPSCs to model PD (including Dr. Gary Ho and Dr. Nikhil Panicker) allowing researchers to test potential new avenues of understanding of PD and treatment.
Commercial stem cell clinics
There are many commercial clinics in the US and around the world that offer stem cell treatments that have not been scientifically proven to work. As stated above, it is important to note that there are currently no FDA approved stem cell treatments for Parkinson’s disease.
A typical treatment at a commercial stem cell clinic involves removing fat cells from the abdomen (some clinics remove bone marrow or blood for this procedure), treating the cells in various ways to isolate mesenchymal or stromal cells from the removed tissue, and finally injecting these cells back into the body. The cells are re-introduced into the body in different locations (into the bloodstream, cerebral spinal fluid, nose, eye, etc.) depending on which disease is being targeted. Such treatments are performed for a fee, sometimes a large one, and are not covered by insurance.
Does it work? Efficacy of commercial stem cell clinics
Commercial clinics do not as a rule publish their results in peer-reviewed journals to demonstrate to the scientific community that the treatments work. Rather, they usually rely on anecdotes from patients as proof of efficacy. Some clinics are tracking their results by measuring variables such as quality of life before or after the procedure. However, without comparing the patients to a similar group that does not receive the treatment, it is hard to know whether any improvement is due to placebo effect or to the treatment itself. Safety data is also limited at stem cell clinics.
Tips & Takeaways:
- There is promise in the use of stem cells as a possible treatment for PD, but more research needs to be done before such a therapy will be approved for clinical use.
- There are various sources of stem cells and each will need to be tested to see which, if any, are useful in treating PD.
- Several small clinical trials have been completed, are underway, or are about to begin, that study the use of stem cell treatments for PD.
- Be cautious of any commercial clinic promoting a treatment that has not been proven by the FDA to be safe and effective.