This is a guest post from The Michael J. Fox Foundation for Parkinson’s Research (MJFF). MJFF is committed to the pursuit of a Parkinson’s cure and better quality of life for those living with the disease today. Stem cells are valuable tools in that work, helping develop new therapies and learn more about the disease. Find out more about the work they do at www.michaeljfox.org.

Parkinson's disease is a neurological disorder that affects one in 100 people over age 60. The disease causes a variety of symptoms including motor problems such as tremors, muscle rigidity and slowed movement, and non-motor symptoms of cognitive impairment, mood disorders, and autonomic dysfunction. It is estimated that nearly 1 million people in the United States and more than 6 million worldwide have Parkinson’s disease. Current treatments can ease some symptoms, but no available therapies stop or slow the progression of the disease.

Scientists are using stem cells to better understand and treat Parkinson’s disease.

Stem Cell Treatments
In Parkinson’s disease (PD), cells that make the chemical messenger dopamine degenerate and die. Introducing new dopamine cells into the brain may help replace what is lost in PD and reduce its symptoms. Such a treatment also could reduce medication side effects. Long-term use of the most commonly prescribed PD medication (levodopa) and progressing disease can lead to dyskinesia or uncontrolled, involuntary movements.

Stem cells can be used in the lab to generate many other types of cells, including dopamine cells. Induced pluripotent stem cells (iPS cells) are derived from adult cells (usually from skin or blood) and can be manipulated to act like stem cells.

In late 2017, researchers in Jun Takahashi, MD, PhD’s lab at the Center for iPS Cell Research and Application at Kyoto University in Japan announced that a study transplanting nerve cells made from iPS cells into the brains of pre-clinical models was promising. The grafted cells were able to secrete dopamine and stimulate neurons in the brain. The implanted cells survived for two years, appeared to improve symptoms and did not cause ill side effects.

In July 2018, the Kyoto researchers announced plans to start a clinical trial moving the procedure into humans. Researchers inject dopaminergic progenitor cells — cells that develop into neurons that produce dopamine — directly into an area of the brain associated with neural degeneration in Parkinson’s disease. The scientists completed the first transplant in October and plan to complete six additional operations by 2022.

In the United States, researchers are looking at other possible therapeutic approaches using stem cells. Lorenz Studer, MD, of Memorial Sloan Kettering Cancer Center, was part of the team that first successfully developed dopamine neurons from human embryonic stem cells. His laboratory is now developing a clinical-grade dopamine neuron cell product made from embryonic stem cells. The cells were successfully grafted in animal models, and the Studer lab will potentially move into human clinical trials in 2019. With backing from MJFF, Ole Isacson MD, PhD, and Penelope Hallet, PhD, of Harvard Medical School are testing other promising stem cell therapeutic approaches using dopamine neurons from iPS cells and embryonic stem cells.

Stem Cells as Tools
Stem cells also can be used to create disease models to learn about the molecular mechanisms of PD and test novel drug molecules.

The National Institute of Neurological Disorders and Stroke at the National Institutes of Health created an open-access repository of engineered stem cells from people with Parkinson’s, individuals with genetic mutations associated with PD (with the disease and at risk), and control volunteers. Researchers are using these cells to investigate the process of Parkinson’s and the role of genetics. They also may be used to screen potential drug therapies.

The Michael J. Fox Foundation also provides stem cells for scientific projects. The MJFF-sponsored Parkinson’s Progression Markers Initiative (PPMI) study makes iPS cells available at no cost to qualified researchers. The study provides more than 130 cell lines from its various cohorts: individuals with PD, control participants, and volunteers at risk for developing PD. When coupled with the deep molecular, clinical, and imaging data collected through PPMI, these cells can be powerful tools for understanding what is different in Parkinson’s and how scientists may address that dysfunction with new treatments.

The Future
Stem cell research could help scientists better define Parkinson’s pathology, screen new drugs and develop new treatments. There are challenges to overcome; work is still needed to generate robust cells, in both quality and quantity that can survive and function appropriately in the brain. Scientists are investigating which source of cells (induced pluripotent or embryonic) is most effective and scientists will ensure any treatment is safe before it becomes widespread.

Momentum is building, though, and greater technology and disease understanding is pushing the field toward new treatments.

Learn more about stem cells from the Michael J. Fox Foundation and the ISSCR.