Making Sense of Stem Cell Therapy for PD

Suketu M. Khandhar, MD Medical Director,

KPNC Comprehensive Mvt Disorders Program

We have long known by the time an individual is diagnosed with PD, they have lost nearly 70-80% of their dopamine producing cells. It is this significant lack of dopamine that leads to the classic motor symptoms of PD and precisely where treatment has fixated for 5 decades. At times it may seem futile to continue supplementing dopamine in a system that is degenerative.

Stem cell therapy is not a new concept. It's been around for years. The idea that we can take precursor cells and redirect them into mature dopamine producing cells is attractive. Why not, as long as it’s safe. It drew the attention of Michael J. Fox to where he appealed to voters and Congress to support stem cell research in 2006.

What are stem cells? Stem cells are cells with the potential to develop into many different types of cells in the body. For our purposes there are 2 main types, embryonic stem cells and adult stem cells. These cells do not have any specific function but can be developed to address specific functions in the body

So why hasn't this caught on? There are many reasons that stem cell therapy has not become mainstream treatment. Cell sourcing, cell line viability, cell survival, cell rejection, lack of standardization towards treatment approach and side effects (esp that of dyskinesia) with possible tumor formation. At this time stem cell therapy for Parkinson's disease is not an FDA approved treatment and not considered standard of care.

There are many for-profit organizations that conduct stem cell therapy for various neurological conditions, some abroad and some local to us in California. These can be expensive with varying results. I would be wary of any program that claims this is “a cure”. Until we have medically reviewed, randomized control trials looking at safety and efficacy in human trials, it's hard to support promoting these programs.

So what is promising? Recently, induced pluripotent stem cells (iPSC) have gained a lot of attention. iPSC are derived from skin or blood cells that can be “reprogrammed” back into an embryologic-like pluripotent state that theoretically allows for an unlimited supply of any type of human cell, in our case dopamine producing cells. It was Professor Shinya Yamanaka, from Kyoto University, who was awarded the Nobel Prize in Medicine (2012) for their discovery.

He was the keynote speaker at the recent World Parkinson Congress held in Kyoto last year.

You may have read about a recent report on a patient by the name of George Lopez (not the comedian) who self funded ($2 million) his treatment working with Southern California researchers and neurosurgeons building on Professor Yamanaka's work. Their goal was to take undifferentiated iPSCs and turn them all into dopamine producing cells, tens of millions of them.

Any leftover undifferentiated cells would have to be eliminated in a safe way. The FDA, under a compassionate use protocol, approved their one-patient study. The surgeons created new experimental instruments to deliver the cells safely into the putamen (a structure that is part of the basal ganglia, close to areas targeted in DBS surgery).

It has been 2 years since the surgery and Mr. Lopez seems to continue to get benefit from surgery via improved motor function. The researchers do not believe they cured him but rather “stabilized” him. They continue to monitor him and routinely get brain scans looking for signs of tumors. When patients ask me about stem cell therapy, I usually refer back to this experiment. The researchers were thoughtful to eliminate undifferentiated iPSCs, thoughtful to use newer instruments to safely deliver the cells and thoughtful to keep Mr. Lopez's safety as a central priority. However, this was a study of one. We can't generalize this to the whole Parkinson population and more experiments on a larger scale looking at long term efficacy and safety are required before this may enter mainstream treatment.

Another promising study was done by researchers at UC San Diego, looking to create a cell line that is lacking a protein called PTB, which was found to influence which genes are turned on vs off. They found in Parkinson mouse models injected with these cells lines, that they were able to increase the number of dopamine producing cells by nearly 30%. That does not sound like much, but it was enough to reduce the motor symptoms of PD in mouse models, restoring dopamine levels to near normal as found in normal mice. The researchers used something called antisense oligonucleotide approach allowing an artificial piece of DNA to bind to the RNA (translators of genetic information) coding for PTB, thereby not allowing PTB to be produced. This particular approach has since been patented with the hope to conduct human trials in the future.

2020 has been a tough year to say the least but it has brought us a better understanding of the utility of stem cell therapy and its hopes for the future.