Ask an Expert: Stem Cell Research and Parkinson’s

Roger Barker is the Professor of Clinical Neuroscience at the University of Cambridge and Consultant Neurologist at the Addenbrooke’s Hospital Cambridge. He is a guest professor at the University of Lund, Sweden and a Principal Investigator in the MRC-Wellcome Trust Stem Cell Institute in Cambridge.

For the last 25 years he has run research that seeks to better define the clinical heterogeneity of two common neurodegenerative disorders of the central nervous system (CNS) – namely Parkinson’s disease (PD) and Huntington’s disease (HD). This has helped him define the best way by which to take new therapies into the clinic. In this respect he has been heavily involved in gene and cell based trials for patients with these conditions and currently co-ordinates an EU funded transplant program using human fetal tissue for patients with PD, following an earlier Medical Research Council (MRC) funded trial using similar tissue in HD. He is part of a new EU project (NeuroStemCellRepair) and a global initiative (GFORCE-PD) that is seeking to take stem cells to trial in these disorders.

First of all, what are stem cells?

Stem cells are cells that have both the capacity to divide and also give rise to differentiated cell types. One example is embryonic stem cells (ESCs) which are found in the newly fertilized egg and which give rise to all the different cells we have in our body.

What is the principle aim of the Parkinson’s research you are currently a part of?

The main aim of my research group is to better define the different types of Parkinson’s disease (PD) that we think exist. From there we try to understand why this may happen and how we can best treat each subtype – including with new therapies such as dopamine cell transplants.

In your research into neuro- degeneration, why is it necessary to use embryonic stem cells?

We use stem cells in two main ways in our research: (i) as a source of cells which we can then turn into dopamine cells lost in PD which we can graft back into the brain to repair this aspect of the disease process. This is mainly done using ESCs. Alternatively, (ii) we have been making patient-derived stem cells (so-called induced pluripotent stem cells – iPSCs) and then turning them into dopamine nerve cells to try to understand what goes wrong in these cells in the disease in that particular type of patient. This also opens up the possibility of testing different drugs on these cells to see if we can slow down or alter aspects of the disease process.

Why do dopaminergic drugs (such as levodopa) fail, or become less effective over time?

Drugs that operate through the dopamine system work well in the early stages of disease. They come in two forms: one that replaces dopamine (L-dopa in the form of sinemet or madopar), or one that stimulates dopamine receptors (dopamine agonists such as ropinirole/pramipexole). Over time, these drugs become less effective as the patient’s own dopamine system continues to degenerate.

In addition, the drugs stimulate the remaining dopamine system in an abnormal non-physiological way (as they are simply taken orally one or more times a day) which leads to the development of side effects, most notably drug induced movements called dyskinesias. These drugs can also produce behavioural and psychiatric problems which in part relate to the fact that they stimulate areas of the brain where dopamine normally works. Thus cell based transplants have the advantage that they could be used for the local delivery of dopamine, released in a normal physiological way at the site it is needed, which may avoid some of these long term complications with the current oral agents we use to treat this condition in the clinic.

How long do you estimate it will take for stem cell treatment for PD to enter the mainstream course of treatment?

It is estimated that stem cell derived dopamine transplants from centres of expertise in this area will come to the clinic in about 2019. If they work in these early trials then it will probably be another 5–10 years before they could enter mainstream use depending on how well they work and ultimately what they cost!

What are some additional barriers that exist for stem cell research and treatment?

The main barriers are:

• the necessary regulation and testing that is required to make sure the cells are safe – and this takes some time to complete;
• the use of stem cells in unlicensed ways in clinics around the world which may derail the work of the whole field (so-called stem cell tourism);
• the ethical concerns and debates about which stem cells are the best to use – and this varies from country to country.

There are a number of studies currently under way at The Barker Lab. Are there any that are particularly promising at this point in time?

Our most promising work at the moment in PD is on translating cell based therapies to the clinic. We are three quarters of the way through a fetal dopamine cell transplant trial and would hope to go to a first in human ESC derived dopamine cell trial in 2019. In addition, we have identified that inflammation may be a driver of disease progression in PD, which may allow us to study anti-inflammatory drugs as a way to slow down the disease process.

Is there anything else you would like to add for our readers and members in Canada?

I think the ability to do research across international borders is now very exciting and is speeding up progress in our understanding and thus treatment of PD. We, for example, work with the team of Francesca Cicchetti at Laval University in Quebec City on blood markers in PD as well as possible new therapeutic agents. Thus, supporting research in one country has an international impact, and it is important for people and patients to understand the difference they make when they help support research in any capacity.

This content was published in the Summer 2017 edition of our quarterly magazine, Viewpoints. The content was accurate as of this publication date.