In mid-July, the American Parkinson Disease Association (APDA) offered a webinar on stem cells and Parkinson’s disease (PD), hosted by Dr. Rebecca Gilbert and featuring Dr. Evan Snyder. They discussed what stem cells are, how they may be applicable to PD, and what research is underway currently. There was also an extended question and answer session. We at Stanford Parkinson’s Community Outreach viewed the webinar and are sharing our notes.
This webinar was recorded and can be viewed here.
If you have questions about the presentation, you can contact the APDA at 800-223-2732 or at firstname.lastname@example.org.
For helpful background on stem cell research, you can also read this APDA article by Dr. Gilbert from 2018.
A similar webinar on this topic was recently offered by the PMD Alliance, featuring Dr. Roger Barker, a scientist in the field. He provides some additional historical context from past research in stem cells. The recording is available here.
Now… on to our notes from the webinar.
Stem cells & Parkinson’s disease – Webinar notes
Presented by the American Parkinson Disease Association
July 13, 2020
Summary by Lauren Stroshane, Stanford Parkinson’s Community Outreach
Dr. Rebecca Gilbert is the Chief Scientific Officer for the APDA. She spoke with Dr. Evan Snyder, an expert on the science of stem cell therapies to potentially treat Parkinson’s disease (PD). He is a professor at the Sanford Burnham Prebys Medical Discovery Institute, where he directs the Center for Stem Cells and Regenerative Medicine.
What are stem cells?
A stem cell is an “undifferentiated” cell, a sort of blank slate that has the capability to develop into various different types of cells. They have the potential to be very useful because they can be isolated to make them easier to work with; they can be transformed in a lab setting into brain cells (neurons) that produce the neurotransmitter dopamine that is deficient in PD; and they offer new methods for studying or possibly treating PD.
There are multiple different sources of stem cells, including those originating from human embryos (called embryonic stem cells) and indecent pluripotent stem cells, which will be explained further.
What are induced pluripotent stem cells?
Induced pluripotent stem cells (IPSCs) are stem cells that are actually created from adult cells, such as from a skin biopsy. In the lab, these regular adult cells can be reprogrammed to become stem cells, which can then be differentiated into various different types of cells, such as dopamine-producing neurons. They have great potential not only for the possible development of new treatments, but also for helping us to understand diseases such as PD on a cellular level.
However, there are significant challenges to using implanted IPSCs to treat PD:
- How do we know which type of cell to use?
- How can we ensure the cells we use are pure?
- How many cells should we transplant, and where in the brain should we implant them?
- How can we ensure that the implanted cells don’t lead to a tumor?
Scientists are working to find the answers to these questions.
Cell-based therapy for PD
In the past few years, there have been some studies of various cell-based therapies for PD around the world. Some showed disappointing or equivocal results about whether this therapy is beneficial, while others are still awaiting results. More clinical trials are being planned.
A trial currently underway in Japan is implanting IPSCs into the brains of PD patients.
What if there were a way to create more dopamine-producing neurons in the brain without implanting new cells? A scientific paper by UC San Diego published this year suggests that a particular protein tells a cell not to turn into a neuron and to be a supporting cell instead. When this protein was suppressed, existing support cells can turn into neurons. The study was done on mice, so we are still a long way from knowing whether it would be possible to use this method to create new neurons in the brain of someone with PD, to replace those that have been lost to disease. Still, it is a very interesting scientific possibility.
Question & Answer Session
Q: I have heard about stem cell clinics outside of the United States that are already treating people with stem cells. Should I consider trying to access some of this treatment?
A: Unfortunately, there are a lot of hucksters out there who think that stem cell biology is simple and that sprinkling stem cells on any disease will result in a cure. In reality, getting stem cells to recreate the actual biological processes we need in order to treat PD is a lot more complicated than that. The clinics who purport to offer these therapies really have no idea if these therapies will work, or if what they are injecting into patients are even truly stem cells. This applies to the use of stem cells claiming to treat any condition right now: they are fraudulent and trying to extract money from you.
In a true clinical trial, the costs of the study will be covered. In a true treatment, the cost of the treatment will be covered by your insurance. If someone is asking you to pay out of pocket for a study or a treatment, it is likely fraudulent and not based in actual science or best practices.
Q: How can I participate in stem cell research?
A: To ensure the findings are accurate, clinical trials are very carefully regulated – by the Food and Drug Administration (FDA), the internal review boards, and by the experimenters themselves. This regulation includes strict guidelines about the criteria for people to be included in (and excluded from) the study. Participants in randomized trials may be assigned to the control group and not even receive the treatment in question. Most of the time, it is not as simple as contacting the research lab and asking if you can be included. That lab might be across the country from you, anyway!
However, if you are seeing a neurologist, let them know that you are interested in participating in research. You may eventually be contacted by a research coordinator to see if you qualify and are interested in a particular study. If so, then you would be informed of any risks involved in the study and consent to participate.
Q: Dopamine is not the only neurotransmitter that is deficient in PD. Will stem cells programmed to become dopaminergic neurons be sufficient?
A: This is an excellent question! We in the field of PD are starting to confront that PD is not solely a movement disorder and not solely a disease of dopaminergic neurons – they are only the first, most prominent target of the disease. Increasingly, science shows that replacing dopamine in those with PD is just the tip of the iceberg. While dopamine replacement therapy such as levodopa has allowed millions of people with PD to enjoy a better quality of life, it does not affect the cognitive or emotional symptoms that can also be an issue.
We still don’t know what the initiating event is that causes PD to develop. Ideally, we would find the “big bang” of PD to understand what precipitates the disease. Stem cells may help us to gradually gain a better understanding of the fundamental science of PD. We need to think bigger and start coming up with therapies to treat the non-motor symptoms.
Q: Will stem cell therapy likely be effective long-term, or only temporarily?
A: This really breaks down into multiple, related questions. If we make neurons that produce dopamine, how long will they produce dopamine for, and how long will they last in the brain? Or will these newer neurons get PD and die off as well?
Based on research in the lab, these cells seem to last a long time (15 to 20 years) and continue producing dopamine. They do not seem to be rejected by our immune system, and they seem to make connections with other neurons in the brain. We do not yet know whether dopamine replacement will ever stop working.
Ultimately, those with advanced PD find that their medications stop working as well. The neurons produced by stem cells function like medication – they help with the symptoms, but do not stop the progression of the disease. Continuing our important research into the fundamental biology of PD – what triggers it to start, and what keeps it progressing over time – is absolutely essential if we wish to find treatments that are truly disease-modifying.
The second part of this question is whether the new neurons can themselves get PD. This is a hot debate in the field currently. From brain pathology of individuals who received stem cell transplants in the 1980s, it’s inconclusive.
Q: How do transplanted cells make neural circuits once they’re implanted in the brain?
A: This is also a really excellent question! It’s not really enough to just stick a nerve cell into the brain and expect it to thrive. Neurons are really like a telephone network; they don’t function in isolation, but make connections with other neurons and communicate with each other constantly. It takes a village!
This field is still very new, but it looks like the fetal tissue cells that were placed in the 1980s have made connections when looked at 15 or 20 years later. It may take a long time, but it does appear that neurons derived from implanted stem cells are indeed able to make connections. We can study how these connections form and function using tracer dyes and other types of tracers to evaluate the kinds of connections that are forming.
Q: Are fetal cells ever being used for this research, and can you explain the difference between embryonic and fetal stem cells?
A: This question gets right to the heart of the debate that stem cell biologists and cell therapists are having in the PD field. Most of us would say that nature is the “gold standard” – everything we do in this field is trying to emulate what nature does best.
Early areas of cell-based therapies was going to fetal cadavers – a fetus that died early inside or outside of the womb – and putting those cells into PD patients. They seemed to work but there were complications, likely in part due to potential contamination or inconsistency between different fetuses. One would probably need 3 to 6 fetuses to provide enough cells to treat one PD patient. Of course, there are often significant ethical concerns to using fetal tissue as well. Fetal tissue comes unpredictably, serendipitously, and is not a reliable source. Given the very large number of PD patients who would need treatments, it was never going to be practical, and scientists sought alternative sources of stem cells.
There is still some research ongoing in Europe using fetal neurons to gain a better understanding of the underlying science.
[Editor’s note: For more information on the differences between embryonic vs. fetal stem cells, check out this FAQ from the Bedford Research Foundation.]
Q: Could umbilical cords be a source of stem cells?
A: It is true that umbilical cord blood and the cord itself does contain some stem cells, though mostly blood stem cells. They are excellent for therapies that are blood-based, such as bone marrow transplants or gene therapies, but in his line of thinking, these cells will not work for neurologic therapies.
Q: Can you elaborate a bit more on the UC San Diego paper from this year that you mentioned previously? Will it have any clinical applications?
A: Glial cells or astrocytes are supporting cells, helping neurons (brain cells) to stay healthy and function well. However, these cells all come from the same type of “grandfather” cell. Maybe we can make the “helper” cells become “worker” cells by suppressing the signal that told them to be helper cells. Theoretically, this would be a drug that the patient would take which would trigger this switch.
It’s a very intriguing idea, but we can’t get too excited until these results are duplicated multiple times elsewhere to validate the research. Only then would we see a clinical trial of this technology.
Q: If a treatment is eventually developed involving stem cells being administered into the brain to treat PD, what would you guess is the time frame for this to be FDA-approved and available to all patients?
A: For this to become standard care, with all the needed clinical trials being done and showing clear results, with no long-term side effects developing in those who have had the treatments, Dr. Snyder would guess at least 10 years. There is a lot still to be done!
Q: Do stem cells need to be from a matching donor, or from the patient themselves? If used from a donor, would the recipient theoretically need to take anti-rejection medication afterward, like in organ transplants?
A: Another fantastic question! There is tremendous debate about these issues among the researchers in this field. Back in the 1980s, they did a wide range of immunosuppression, ranging from none to organ transplant-level. From these experiences, it appeared that only minimal immunosuppression was needed, maybe just for a few months, if that.
We now know that the brain is not “immune-privileged” and can be susceptible to immune attack. There are various different regimens being studied. We will also need to determine what the likelihood and risks are of an immune reaction. It won’t be cost effective or practical to have an individual cell bank for each PD patient seeking treatment, so stem cells would need to be standardized and controlled so they work for everyone.