Parkinson’s disease stem cell therapy research update

When I first started The Niche more than a dozen years ago, I hoped we’d see a Parkinson’s disease stem cell therapy by now. A proven one.

I was a little too optimistic back then. Now in 2022, I know much better how hard translation to the bedside can be in general. Still, I’m hopeful. It’s just that the timeline is always much longer than you think.

In this post, I give an update on this research area and explain why I am optimistic in the long run.

Parkinson’s disease stem cell therapy

In the stem cell field, there are some diseases where the road from research to therapy should be a relatively straight line. That seems the case for stem cells for Parkinson’s.

Why do I say that?

We know the specific cells that are lost in this disease and researchers can now efficiently make those cells in the lab. Together that’s a great foundation for therapy development. As I’ll talk about later, the stem cell field doesn’t have such a foundation for most other diseases.

The neurons for Parkinson’s can be made in both autologous and allogeneic forms so a self-transplant is even possible.

Even with this strong foundation, putting this all together into a safe and effective treatment is still very difficult.

Relative optimism in the long haul

Even so, I’m more optimistic here than in some other areas of stem cell translational research.

For instance, when we look at the arena of stem cells for COPD, which often includes no actual stem cells, most of what is going on is not approved by the FDA. Some of it is probably illegal. It’s not even clear to me how stem cells in most cases would help COPD.

The cell therapy and stem cells for autism space is extremely active even commercially at clinics, yet we mostly don’t even know what causes autism and it is a highly heterogeneous collection of conditions. Here again, we have many folks doing stuff they shouldn’t too.

Another example is the field of stem cells for heart disease, which has been wracked by controversy and misconduct.

By comparison, the arena of stem cells for Parkinson’s is in a much better position in almost every way. I’m also relatively optimistic about stem cells for macular degeneration and stem cells for diabetes over the long run.

How would Parkinson’s disease stem cell therapy work?

The basic idea is that human pluripotent stem cells like iPS cells or ES cells would be differentiated in a precise way in the lab.

This process produces human dopaminergic neurons, the cell type lost in Parkinson’s disease.

These cells would then be transplanted into the proper location in the brains of patients and take the place of the lost cells. In Parkinson’s specific neurons are lost in the substantia nigra so that generally is one prime target for transplantation but not the only one.

The hope is that these new cells would be functional and not cause problems. What are the risks? For example, if the transplanted cells produce too much dopamine or in the wrong place, they can cause trouble like movement disorders called dyskinesias beyond or different from what the patients are already facing with Parkinson’s in terms of movement issues.

Note that the underlying cause of Parkinson’s isn’t well-understood. It’s thought to be a combination of environmental and genetic factors, leading to dopaminergic neuron death. Such a brain environment could eventually damage or kill transplanted dopaminergic neurons too. This represents another possible challenge.

Stem cell clinical trials for Parkinson’s

Previously, some researchers transplanted fetal brain tissue into Parkinson’s patients. In some cases, it seemed to produce lasting improvements in symptoms in some patients, but double-blinded studies didn’t support this as a generally viable approach.

Where do things stand now?

I found 37 trial listings on stem cells for Parkinson’s on Clincialtrials.gov, which sounds like a lot. However, unfortunately, almost none of these are real, robust interventional trials based on solid preclinical data. Many have unknown status, have been terminated, or are using MSCs or mesenchymal cells or bone marrow cells, which doesn’t make sense to me. Some are for-profit clinic-type operations too, which is troubling.

What are some of the more promising trials or efforts that will lead to trials? I can’t list them all but here are the ones I’ve been following most closely:

• The MSK Parkinson’s disease trial looks interesting. Viviane Tabar and Lorenz Studer are co-leading this trial on testing injections of stem cells into the brain for Parkinson’s. This is the BlueRock Therapeutics trial. I can’t wait to see the results.
• Jun Takahashi has an iPSC-based trial ongoing in Japan for Parkinson’s. I’m excited to see those results in a couple of years too.
• Other potentially promising stem cell-related Parkinson’s disease efforts are in the works too. Jeanne Loring founded Aspen Neuroscience, which is working in this area. I expect they’ll start a trial in 2023 or 2024.
• Malin Parmar leads a team that has a future trial planned too.

Overall, while this road is not as straightforward as I thought back in 2010 when I started The Niche, I believe we’ll get there. Whether it is iPSC-based or ESC-based, autologous or allogeneic, I don’t know, but it’s going to happen.

References

• Mayo Clinic page on Parkinson’s disease.
• Review on stem cell therapies for Parkinson’s.
• Another review on Parkinson’s disease stem cell therapy and other cell therapies.
• Stem cells for Parkinson’s trial search data on Clincialtrials.gov