With two recent publications in the journal Nature reporting promising early results on the use of stem cells for treating Parkinson’s, we wanted to provide an update on this closely watched area of treatment — and an overview on what’s on the horizon for stem cell and other cell-based therapies. 

Parkinson’s is marked by the loss of cells that produce dopamine, a neurotransmitter that helps control movement. Replacing those lost cells with new, healthy ones has been a focus of research since the 1980s, with efforts to transplant healthy dopamine cells and tissues. In the 1990s, stem cell technologies advanced and with it, efforts to create replacement cells for people with PD. Today, the search continues for a way to use stem cells to generate production of healthy dopamine-producing cells through multiple ongoing clinical trials. The Michael J. Fox Foundation (MJFF) was an early supporter of much foundational work in this area and has continued to monitor progress in these approaches. 

We talked with Brian Fiske, PhD, chief scientist at MJFF, about the current state of cell-based therapy for PD and what the future might hold. 

MJFF: Why are cell-based therapies, and particularly stem cells, a focal point in the search for better Parkinson’s disease treatments? 

Dr. Fiske: 

People with Parkinson’s progressively lose the cells in the brain that produce dopamine. These are not the only cells that degenerate in PD, but not having enough dopamine underlies many Parkinson’s movement-related symptoms, including the rigidity and slowness of movement that affect so many people with the disease. 

Replacing these lost cells could potentially fix this problem and researchers have been exploring ways to do this for many years, initially with tissue-based replacement but later with the use of stem cells. Stem cells are exciting because they hold the remarkable ability to develop into different types of specialized cells in the body. Some of MJFF’s earliest funding supported researchers to explore and develop recipes for coaxing stem cells to become dopamine-producing neurons that could potentially be used as replacement cells and hopefully alleviate PD movement symptoms.  

Research to generate replacement cells for neurodegenerative disorders like PD started back in the late 1990s after human stem cells were first isolated. Today, the therapies being developed use embryonic stem cells or, more frequently, induced pluripotent stem cells (iPSCs), which are often generated by reprogramming skin cells to become brain cells. This latter approach actually led to the scientists who developed the method receiving the Nobel Prize in 2012 for their discovery. 

These stem-cell based cell replacement approaches, which are sometimes categorized as a type of regenerative medicine, may hold potential to benefit people with Parkinson’s. However, it’s important to keep in mind that in their current forms, they’re not curing the disease. That is, they are offering the brain an additional source of dopamine to help address some of the movement problems associated with the disease, but they may not affect nonmotor symptoms and are not directly targeting the underlying disease process, which may still be continuing to progress in the background. 

MJFF: What should people know about the status of stem cell-based replacement therapy for treating Parkinson’s? 

Dr. Fiske: 

While there were a few case reports of people benefiting, prior attempts to transplant dopamine-producing cells and tissues into the brains of people with PD generally were not successful. Now, newer approaches are underway using improved methods and advanced technologies which may give us the clearest picture yet of possible benefits. Clinical trials are mostly in early stages to test their safety and efficacy, and results so far involve just a handful of participants. Larger trials in which more people receive these experimental therapies still are needed. A number of groups are currently leading the charge in testing dopamine cell replacement therapies: 

Testing on bemdaneprocel, an embryonic stem cell-derived therapy, is advancing through clinical trials. As reported recently in Nature, bemdaneprocel posed no safety concerns 18 months after being surgically placed into the brain, and there were positive trends related to the treatment of motor impairments in people with PD, although importantly the study was not designed to demonstrate definitive benefits given its small size and lack of a control group. Based on these outcomes and discussions with the U.S. Food and Drug Administration, the drug’s manufacturer, BlueRock, has indicated they plan to move directly to a Phase III study for expanded evaluation of the effectiveness of bemdaneprocel.

A team at Kyoto University recently reported promising 24-month, post-transplantation results in Nature. The cell replacement therapy, comprising dopamine-producing neurons derived from iPSCs, raised no safety concerns and also appeared to hold potential for reducing motor impairments in PD. Sumitomo Pharma, which has had a long-standing partnership with the researchers in Kyoto, is commercializing the iPSC-based approach for PD in Japan and the United States.

RNDP-001, another iPSC-based approach for cell replacement in PD, is currently in development. MJFF is also supporting a component of the program created by the manufacturer, Kenai Therapeutics, to test RNDP-001 in people with certain genetically inherited forms of PD (e.g., PRKN mutations) based on beliefs that these individuals may be particularly responsive to such an approach.

An iPSC-based approach, ANPD001, is being tested in an early safety trial in people with PD. Interestingly, the company, Aspen Neuroscience, is using a so-called autologous approach, in which cells are generated from the patient directly. Other groups are using an allogeneic approach, in which cells come from other donors. Whether one or the other approach will prove more beneficial (and feasible) will be an important question we will be monitoring as these programs continue clinical testing. 

MJFF: What are some of the other ways researchers are using cell-based therapy for PD? 

Dr. Fiske: 

Cell-based therapy also can be applied with the idea of protecting existing brain cells so that they don’t become as damaged or dysfunctional as PD progresses. Researchers have many theories for how such cells might help, for example by producing factors that modulate the immune system or so-called neurotrophic factors that promote the growth and survival of neurons in the brain. As an example of this approach, MJFF funded researchers at UTHealth Houston led by Mya Schiess, MD, who has been testing an intravenous infusion cell protection therapy that is based on mesenchymal stem cells. Derived from bone marrow, mesenchymal stem cells have special properties and may secrete anti-inflammatory molecules and growth factors. 

MJFF: As you track clinical trials, how do you view the landscape today for cell-based therapy?  

Dr. Fiske: 

We increasingly see robust clinical data suggesting the potential benefits from cell replacement approaches. These programs need to advance further in the clinic to get better data, but certainly they’re showing safety and possibly some signals suggesting cell-based replacement therapy might reduce some of the movement symptoms for people with Parkinson’s. What remains a big unknown is how the risks, costs and benefits measure up against current and emerging levodopa-enhancing treatments and neuromodulation (e.g., deep brain stimulation) approaches that also treat Parkinson’s movement-related symptoms. 

The research on the use of stem cells for general cell protection remains more uncertain and there is yet clear and consistent data on whether these approaches will offer real benefit. 

Overall, what we’re looking for is a powerful proof of concept in the clinic, and so we're excited to see approaches moving into clinical testing. This testing helps us understand the level of benefit these approaches might provide for reducing symptoms. Should things continue to advance in a positive direction, we are likely to see a lot of innovation around additional ways to deliver stem cells as well as different cell types that could be delivered besides the dopamine-producing cells. The current Parkinson’s therapeutic pipeline is really robust, and it holds a lot of hope. I think stem-cell based treatments are one potential component of that hope. 

MJFF: There have been reports of clinics offering stem cell treatments outside of research at a cost to patients. What should people know about these unregulated treatments? 

Dr. Fiske: 

Researchers continue to advance clinical trials of stem cell therapies for Parkinson’s, but as of today, there are no established, FDA-approved stem cell therapies for the disease. 

Some clinics around the world offer unregulated cell therapies directly to patients with limited information on what is being delivered or long-term safety and benefits. People seeking out such treatments really should speak with their doctors and carefully weigh the potential risks.  

To learn more: 

Connect to more information at michaeljfox.org/stem-cell-research-and-parkinsons-disease. 

Listen to a podcast on stem cells with Chief Scientist Brian Fiske, PhD, and Harini Sarva, MD, director of the Parkinson’s Disease and Movement Disorders Center, associate professor of clinical neurology and lead clinical trialist for movement disorders at Weill Cornell Medicine. She is also a principal investigator of the clinical trial on the stem cell-based therapy bemdaneprocel for Parkinson’s disease. 

Keep up with future updates on stem cells therapy for PD by subscribing at michaeljfox.org. 

Learn about any opportunities to participate in research involving stem cells at foxtrialfinder.org.