Parkinson’s occurs as a result of the gradual loss of dopamine-producing cells (neurons) in the brain. It is hoped that stem cell therapy (also known as cell replacement therapy) may provide the elusive treatment that either halts the progress of the disease or provides a cure. Current therapies treat the symptoms of Parkinson’s but their effects are not always long lasting and they may also bring with them unwanted side effects. Success with stem cell therapy would represent a significant advance in treating the condition.
What are stem cells?
Stem cells are a class of immature cells that are able to differentiate, or mature, into specialised cell types. They are found in many parts of the body. In nature, stem cells come from two main sources: embryos (embryonic stem cells), and adult tissue (adult stem cells), and are generally characterised by their potential to differentiate into particular cell types, such as skin, muscle or bone. In recent years, stem cells have also generated mature, specialised cells such as skin cells.
As well as the ability to ‘differentiate’ into another cell type with a specialised function, stem cells are also characterised by the fact that they are able to divide and multiply to form copies of themselves.
These two distinct properties mean stem cells can serve as an internal repair system, dividing without limit to replenish other cells.
Stem cell research and Parkinson’s
The aim of stem cell research in Parkinson’s is to understand how nerve cells develop, why some die and how healthy cells can be used to replace damaged brain cells. With this knowledge it may be possible to replace the damaged cells in the brain by introducing healthy dopamine-producing cells generated from stem cells grown in the laboratory. Healthy dopamine-producing cells derived from stem cells could also be useful to researchers in testing new treatments.
Researchers are particularly interested in embryonic stem cells as they have the potential to develop into all types of cells in the body, including the brain. More research is needed in order to understand the way these cells work to ensure that replication can be controlled and a safe treatment developed.
Where do stem cells come from?
Various types of stem cells are found at different stages of human development and in different parts of the body, all of which are of interest to researchers.
Embryonic stem cells: these stem cells are found in fertilised eggs that are only a few days old. These are the only cells that can develop into any type of cell within the body. The abundance of stem cells decreases as the embryo grows and stem cells become specialised cell types that form parts of our body.
Whilst embryonic stem cells are very promising as a treatment for Parkinson’s, they also have the risk of uncontrolled growth in the body which could lead to the formation of tumours. Much more research is needed in order for scientists to understand how stem cells work and how they may be used to produce treatments for Parkinson’s and many other medical conditions.
Adult stem cells: although adult stem cells exist, they are found in quite small numbers in certain parts of the body and do not multiply quickly. Adult stem cells have been used to treat some conditions – for example bone marrow transplants to treat leukaemia. However, it is not currently possible to change adult stem cells into nerve cells suitable as a treatment for Parkinson’s.
Induced Pluripotent Stem Cells (iPS cells): in 2007 scientists discovered how to ‘reprogramme’ specialised adult cells in the laboratory so that they would act like embryonic stem cells. These are known as induced pluripotent (iPS) cells. Like embryonic stem cells, iPS cells have the ability to develop into the cells of any organ or tissue, although they sometimes behave slightly differently. The techniques used to create iPS cells still need refinement before they can be used for safe and effective therapies. iPS cells are not identical to embryonic stem cells and any differences need to be carefully explored and understood.
In order to be used successfully, the DNA in the adult stem cell must be permanently changed to turn it into an iPS cell. At the moment, scientists don’t know if this causes any long-term harmful effects. Cells made from iPS cells might not be stable over long periods of time and may change again to form other types of cell. The initial experiments used viruses to import the new genes into cells which risks changing the cells into cancer cells. However, more recent research indicates that it may be possible to generate iPS cells without the use of viruses, which would be a much safer approach.
Bone marrow: these stem cells are found in our bone marrow and bones.
Umbilical cord blood: during pregnancy cells from foetal bone marrow move into the umbilical cord and placenta. Umbilical cord blood represents a potential source for blood stem cell transplantation but this is most commonly utilised in children. At present there is no evidence to support umbilical cord blood as a sources of stem cells to repair dopamine-producing cells in the brain of people with Parkinson’s.
What are ‘stem cell lines’?
A stem cell line is a family of constantly dividing cells, the product of a single parent group of stem cells. They are obtained from human or animal tissues and have been manipulated in a laboratory so that they have the ability to divide almost indefinitely, creating the line.
Because stem cell lines produce so many copies of themselves (dividing almost indefinitely), this means that scientists have a large ‘bank’ of cells for their research and are less likely to need to take cells from an embryo repeatedly. Of course, it is important that researchers are also able to stop such cell lines dividing at some point so that they can generate tissue specific cells, such as for the brain in the case of Parkinson’s treatment. The challenge for researchers is to discover how they can control the process which causes stem cells to differentiate.
What is cloning?
Cloning refers to the process of making a genetically identical copy of an animal by replacing the DNA found in an unfertilised egg with the DNA found in an adult cell. This produces a genetic replica of the adult cell and is important in research for two main reasons:
- therapeutic cloning- this aims to produce embryonic stem cells which are grown in a laboratory and can be used to replace or repair damaged tissue. This is fundamentally different in process and purpose from reproductive cloning, although there may be a general misconception that both are the same
- reproductive cloning- this is used to create a genetic duplicate of an existing organism. Reproductive cloning is only legal in animals and is strictly illegal in humans. The cloned embryo is placed in the womb of the mammal until birth, as in the case of Dolly the sheep in the UK.
When will stem cell (cell replacement) therapy be available as a Parkinson's treatment?
Whilst there has been considerable progress in stem cell research in the last decade, particularly for the treatment of blood and immune system disorders, scientists are still some way from being able to start clinical trials using stem cell therapy for Parkinson’s. No-one can predict how long it is likely to take for stem cell therapy to be a viable treatment for Parkinson’s.
Also, even if a therapy is approved, it is unlikely to work for everyone just as no one medication is suitable for everyone.
At this stage, scientists do not know which type of stem cell, if any, may eventually lead to a successful treatment or cure.
The key challenges for scientists at present are:
- to understand the way cells grow and differentiate
- to identify methods to differentiate the stem cells into the cell types needed in the brains of people with Parkinson’s
- to establish the best ways of getting stems cells into the right part of the brain.
It is worth pointing out that brain implants using foetal brain material are not the same as stem cell research. They are both types of neural replacement therapy but the techniques and the material used are different.
Foetal brain implants use developing cells extracted from aborted foetuses which are already programmed to become dopamine cells, unlike stem cells which are as yet unspecialised. It is hoped that such implanted cells will connect with other cells in the region of the brain they are implanted in and start producing enough dopamine to correct the problems that result from a shortage of dopamine.
So far, results have been mixed, partly because it is difficult to control the amount of dopamine produced and partly because it is impossible to ensure that cells used for implantation are standardised. Scientists hope that stem cells will make it possible to produce large amounts of dopamine-producing cells that can, importantly, be both controlled in terms of dopamine production and also standardised to ensure reliable outcomes.
Legal and ethical questions
Stem cell research and treatment is a matter of considerable debate and many people are opposed on ethical grounds, although others believe that the benefits of such research far outweigh ethical concerns. There is strict regulation in all European Union Member States and many other countries to ensure that research is carried out legally and ethically.
Opposition to research using cells from an embryo tends to arise due to:
- the belief that embryonic stem cell research involves the destruction of the earliest developing cells and some regard this as destroying a human life
- concern about the creation of embryos with the intention of destroying them once certain cells have been extracted
- objections to any kind of genetic research, which is perceived as undermining human dignity and interfering with nature.
Fortunately new techniques are being developed which will enable researchers to extract embryonic stem cells without destroying an embryo. But this will no doubt remain an area of controversy and personal opinion for some time.
The improvements achieved in the field of Induced Pluripotent Stem Cells (iPS cells) is likely to make them the stem cell type of choice in the future, although iPS clinical trials are probably further away than trials using embyronic stem cell therapies.
Content last reviewed: June 2015
We would like to thank Professor Anders Björklund (Lund University, Sweden) for his help in reviewing this information.
- 'Cell Replacement Therapy For Parkinson’s Disease And The Future Of The Brain'