Stem Cell Therapies for Parkinson's

Although the underlying cause of Parkinson's disease is unknown, scientists do know which cells and areas of the brain are involved. Researchers are already using stem cells to grow dopamine-producing nerve cells in the lab so that they can study the disease, especially in those cases where there is a known genetic cause for the condition. Because a single, well-defined type of cell is affected, it may also be possible to treat Parkinson’s by replacing these lost nerve cells with healthy new ones.

A new study, TRANSEURO, and which has been part-funded by CPT, is looking at foetal human dopamine transplants and aims to address issues of consistent efficacy and avoiding the side effects of the involuntary graft induced movements. This new study will involve a new clinical trial.

Scientists remain optimistic that introducing young cells into the brain could better treat Parkinson’s disease, but not enough foetal tissue is available to treat the large numbers of people with Parkinson’s, and the use of foetuses also raises ethical questions. So at the same time, they are looking at stem cells as an alternative source of new dopamine cells for Parkinson’s patients:

Embryonic stem (ES) cells could be directed to make dopamine-producing neurons, which could be transplanted into patients. Dopamine-producing neurons have been made from both mouse and human embryonic stem cells in the laboratory, and the human cells have recently been shown to have similar effects as the foetal cells in a rat model of Parkinson’s disease. Induced pluripotent stem (iPS) cells could be made from a patient’s own skin cells in the lab, and then used to make dopamine-producing neurons. More studies are needed to make sure the cells are safe and would not go on to cause tumours in the brain, and also do not rapidly develop the pathology of Parkinson’s given they are derived from the patients themselves.

Understanding the disease and developing new drugs:

Transplantation is not the only application for stem cells. Scientists are making iPS cells from patients with Parkinson’s disease, and using these stem cells to produce diseased neurons in the lab. The neurons act as a powerful tool to study how Parkinson’s disease works and to test substances that could be developed into new drugs to treat the disease.

Current research:

Stem cell treatments for Parkinson's are still in the early stages of development. Some of the most important recent advances include work on methods for making dopamine-producing neurones in the lab; research on how to improve the effectiveness of transplants and avoid side effects; and studies investigating how the disease develops and how cells can help with the development of new drugs to stop this.

Cell replacement research - some recent examples:

USA-based researcher Lorenz Studer and his colleagues have recently succeeded in making highly efficient dopamine-producing neurons from human embryonic stem cells and have transplanted them into the brains of rats and mice with a dopamine lesion (to mimic the features seen in Parkinson's disease). The cells did not multiply abnormally and improved some features in the mice. The researchers also transplanted the neurons into monkeys to show that they would survive and function in larger animals. Work is needed before tests can begin on human patients: the neurons need to be made in sufficient numbers to be effective, and produced in a way that ensures the cells are safe and of the right clinical grade. The scientists hope early clinical trials may be able to start in 2017-18.

Malin Parmar and others in Sweden and Italy have taken human skin cells and converted them directly into dopamine-producing neurons. Whether these neurons survive and improve the features of the disease when transplanted into an animal is not yet known. The long-term goal is to make dopamine-producing neurons from patients' own skin or hair cells.

Disease and drug research - a recent example:

Scientists are using iPS cells to investigate the genetic problems that make some people susceptible to Parkinson's. Tilo Kunath’s research group in Edinburgh is doing this by making iPS cells from a mother and daughter with a known genetic cause of PD. The mother has Parkinson’s, but her daughter did not inherit the genetic problem. By comparing the ability of the different iPS cells to make neurons and examining those neurons closely, the researchers hope to discover more about how the disease works and to find new drugs to treat it.

The road to therapies

Stem cell therapies for Parkinson’s disease are not yet ready for use in patients. Much work still needs to be done before clinical trials can go ahead.

The main challenges for scientists are:

  • To identify the type of cell that has the most potential for research and new treatments. So far, researchers have had most success making dopamine-producing neurons from embryonic stem cells, but it is not yet clear whether the lab-grown neurons are close enough to naturally produced nigral neurons to succeed as therapies.
  • To find out how to grow neurons in sufficient quantities and at high enough safety standards to treat patients.
  • To establish exactly how and where to transplant the cells so that they work properly in the brain without causing side effects.

This article has been compiled using excerpts from EuroStemCell - Stem Cell Factsheets

Further Reading:

'Parkinson's Cell Transplants Show Good Innervation After 24 Years' news article May 2016.

Scientific papers: Parkinson's disease induced pluripotent stem cells - Nature Communications 2, Article number: 440

Image courtesy of Tilo Kunath Ediburgh University