Stem Cells Generating Dopamine Neurons in Brains Affected by Parkinson’s

“You have Parkinson’s.”

Sixty thousand Americans hear this life-altering sentence from their doctors each year, and the impact of this chronic neurodegenerative disease is expected to increase with an aging world population caused by climbing life expectancies (Downward & Pool). However, stem cells, specialized cells that can “divide indefinitely,” have the potential to repair brain damage caused by Parkinson’s Disease. While stem cell treatment would not be a permanent cure nor would it relieve all symptoms, patients could potentially live 20 to 30 years longer with a significant increase in “mobility and function” without the intervention of any medication (Denworth, 2015). 

The exact cause of Parkinson’s is unknown; however, the loss in production of the neurotransmitter dopamine is a substantial factor. Dopamine is produced in the substantia nigra, a movement-controlling region of the brain, where nerve cells are located. If around 80% or more of these nerve cells stop functioning properly, the symptoms of Parkinson’s begin to unveil themselves (“Parkinson’s Disease,” American Association of Neurological Surgeons). One of the main functions of dopamine is to send messages to the movement and coordination-controlling region of the brain. Scientists have also found that patients with Parkinson’s produce less of the neurotransmitter norepinephrine and Lewy bodies — clumps of protein within neurons. One of the functions of norepinephrine is to regulate “the circulation of the blood.” Parkinson’s patients typically experience fluctuating blood pressures due to low amounts of norepinephrine, which causes weariness and lethargy (Brazier, 2018). The symptoms of Parkinson’s vary depending on the individual, but the most common symptoms include involuntary hand tremors, loss of balance, inability to perform learned automatic tasks quickly, loss of defined facial expressions, slurred speech, and handwriting changes (“Parkinson’s Disease,” Mayo Clinic).


Figure 1 from National Institute of Environmental Health Sciences (NIEHS): This diagram shows the difference between a healthy brain and the brain of someone affected by Parkinson’s disease. The diagram depicts how there is a dopamine shortage in the brain of a Parkinson’s patient, which ultimately leads to the disease.

The most common medication for Parkinson’s is Levodopa, which helps Parkinson’s patients make dopamine since their dopamine-producing brain cells are deficient. However, Levodopa has a large number of side effects despite the significant amount of improvements that have been made since its initial release. A primary complaint of patients taking Levodopa is intense nausea, which occurs because Levodopa does not go directly to the brain where it is needed but is instead “absorbed in the small intestine and makes its way into the bloodstream.” The Levodopa within the bloodstream then crosses the semi-permeable “blood brain barrier” before entering the brain. The feeling of nausea is the result of a protein called DOPA decarboxylase. This protein converts Levodopa into dopamine both inside and outside the brain, with the latter causing the sensation of nausea. Further improvements have been made to the drug to mitigate the amount of dopamine created outside the brain by DOPA decarboxylase. However, these improvements are negligible when considering the fact that higher doses of Levodopa are required as the severity of Parkinson’s increases over time (Port, 2017).

Medical technology is improving day by day, and it is exciting that scientists may be on the brink of a medical breakthrough for Parkinson’s. A neurosurgeon named Ivar Mendez experimented with stem cell treatment on a man with Parkinson’s by inserting “dopamine cells from a fetus” into his brain. Eight years later, the man went from being unable to stand to walking perfectly. The move was controversial since the stem cells were harvested from “aborted fetal tissue.” Nonetheless, further testing in animals has continued to rely on “stem cells derived from human embryos and adult skin cells” despite ethical concerns. In 2007, a Japanese biologist team was able to revert skin cells found within adult mice to embryonic stem cells that, in turn, can be transformed into any type of cell (Denworth, 2015). In 2017, Kyoto University in Japan announced that researchers had successfully extracted human induced pluripotent stem cells (iPS) from both healthy patients and Parkinson’s patients. These cells were then used to treat primates with Parkinson-like symptoms. After two years, the primates experienced an increase in dopamine levels, remained tumor free, and showed movement advancement (Hirschler, 2017). In 2018, Japan started a clinical trial on humans for patients with Parkinson’s using iPS cells. The researchers will “inject dopaminergic progenitors” which are formed from iPS cells into human participants. The hope is that dopaminergic neurons will form from the progenitors as they did in trials with primates. The Japanese research team plans to use seven human subjects, inject them with iPS cells, and monitor them for two years (Normile, 2018). 


Figure 2 from Tomorrow Edition: The diagram above depicts the process of two different methods of the implantation of stem cells in Parkinson’s disease patients: embryonic stem cells and induced pluripotent stem cells. 

Although researchers are years from declaring stem cell treatment a readily viable option for Parkinson’s, it is exciting to see how the cure may lie right within our own skin cells. Progress-permitting, Parkinson’s patients can look forward to living a completely normal life in the near future.

Edited by Sarina McCabe

References:

Brazier, Y. (2018, October 19). Parkinson’s disease: Early signs, causes, and risk factors. Retrieved October 12, 2019, from https://www.medicalnewstoday.com/articles/323396.php.

Denworth, L. (2015, April 1). Stem Cells Could Repair Parkinson’s Brain Damage. Retrieved October 12, 2019, from https://www.scientificamerican.com/article/stem-cells-could-repair-parkinsons-brain-damage/.

Downward, E., & Pool, J. J. (n.d.). How Common is Parkinson’s Disease?: Parkinson’s Statistics. Retrieved October 12, 2019, from https://parkinsonsdisease.net/basics/statistics/.

Hirschler, B. (2017, August 31). Human Stem Cells Fight Parkinson’s Disease in Monkeys. Retrieved October 12, 2019, from https://www.scientificamerican.com/article/human-stem-cells-fight-parkinson-rsquo-s-disease-in-monkeys/.

Normile, D. (2018, July 30). First-of-its-kind clinical trial will use reprogrammed adult stem cells to treat Parkinson’s. Retrieved October 12, 2019, from https://www.sciencemag.org/news/2018/07/first-its-kind-clinical-trial-will-use-reprogrammed-adult-stem-cells-treat-parkinson-s.

Parkinson’s Disease. (n.d.). Retrieved October 12, 2019, from https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Parkinsons-Disease.

Parkinson’s disease. (2018, June 30). Retrieved October 12, 2019, from https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055.

Port, B. (2017, October 9). How do levodopa medications work? Retrieved October 12, 2019, from https://medium.com/parkinsons-uk/how-do-levodopa-medications-work-ac6a6e58e143.

Image References: 

Parkinson’s patients have less dopamine [Graphic]. Retrieved from https://www.niehs.nih.gov/health/topics/conditions/parkinson/index.cfm

Parkinson’s disease patient [Graphic]. Retrieved from https://tmrwedition.com/2017/09/13/cell-replacement-therapy-for-parkinsons-disease-and-the-future-of-the-brain/

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