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  • Writer's pictureMark Mardell

Cell Therapy

Updated: Apr 29

From levodopa to Deep Brain Stimulation (DBS) we're all pretty familiar with the treatments for Parkinson's. But could there be something, just around the corner, that could change the whole game, not just stalling but reversing the tide of symptoms? That's the subject the Movers and Shakers are discussing today as they gather in the Notting Hill pub with special guest Professor Roger Barker, a world-leading expert on the application of stem cells as a potentially revolutionary treatment for Parkinson's.

By Podot


Each week Rory Cellan-Jones guides us between the laughs and moans in the pub. To read Rory's summary of this week's episode click here.

 

Watch Behind the Scenes with Roger A Barker



 

Guest Biography

Roger A Barker

Roger A Barker is the Professor of Clinical Neuroscience at the University of Cambridge and an Honorary Consultant in Neurology at Addenbrooke’s hospital in Cambridge. He undertook his undergraduate studies in Oxford University and his clinical training at St Thomas’ Hospital in London. He then completed his general medical training before undertaking a PhD in Cambridge looking at repairing the brain in Parkinson’s disease using cell therapies. Since then he has gone on to work on novel cell and gene therapies for PD as well as related condition Huntington’s Disease (HD). He has completed 2 gene therapy trials in PD, 2 cell therapy trials in PD and a cell therapy trial in HD. He has also undertaken small molecule and drug repurposing trials in HD as well as epidemiological studies describing the natural history of PD and its subtypes- subtypes that he then marries up to these new therapies. He has been a Director of the International Society for Stem Cell Research and is the new President of the World Parkinson Coalition. He has published extensively and is heavily involved with the Cure Parkinson charity.


 

Dopamime Cell Therapies for Parkinson's Disease - Is this a pipe dream?

By Roger A Barker


The idea that you could repair the brain in Parkinson’s disease (PD) has long been considered and some successes have been achieved over the years using this approach, but also there have been many failures. However, in 2024 we are just entering an exciting new phase where a range of human stem cell derived dopamine cells are transitioning into clinical trials in people with Parkinson’s (PwP) for the first time.


The basic concept is to replace the dopamine cells lost in PD with a new set and by so doing repair a critical site of pathology, namely the nigrostriatal dopaminergic pathway which is currently targeted therapeutically with oral dopamine drugs and neurosurgical interventions. In the human brain, there are between 400,000 and 500,000 dopamine cells within the midbrain (including the substantia nigra- a site of major pathology in PD) and when one has lost half of these cells, the first symptoms and signs of PD emerge. The importance of this pathology to the problems of early PD is evidenced by the fact that dopamine drugs work very well in ameliorating these clinical features although with time side effects emerge due to off target effects and the non-physiological stimulation of the pathway by drugs taken orally.  All of which means that if you could graft in about 200,000 new dopamine nerve cells then many of the early features of PD should go away without the need to take drugs which brings with it the added advantage that you would avoid all the long term side effects.

The most successful, and in fact original, approach to achieving this used the developing dopamine cells collected out of the brain of fetuses collected from termination of pregnancies. In this work, fetal material was collected and the developing midbrain (or more correctly named, human fetal ventral mesencephalon; hfVM), that contains the nigral dopamine cells that are lost in PD, dissected and partially processed to give a cell suspension that could then be injected into the brain. In order to make sure enough dopamine cells survived this procedure, the developing midbrain from at least 3 fetuses was needed per side of the brain grafted and these could only be collected and stored for a few days. The tissue was then injected into the brain of a PwP at the site where dopamine normally works- the striatum- and in some cases the results were dramatic. On scanning, the patients dopamine levels went back to normal and they could stop taking their anti-PD medication as they were clinically so much better, albeit a benefit that took at least a couple of years to be maximal, given the grafted cells had to survive and then innervate the brain of the PwP.


However, despite these proof of concept successes, the results were too variable to make this a reliable therapy that could be recommended for clinical adoption. Thus attempts were made to try and control the factors that were thought to account for the variability, and this led to a new and recently completed trial called, TransEuro. However, this trial showed that using human fetal material was never going to be the way forward (irrespective of the ethical issues intrinsic to its use) for logistical supply reasons as for every patient transplant, another 7-8 surgeries were cancelled because of a lack of tissue. As such another cell source was needed that could be more relied upon and in 2011-2012 it was discovered independently by 2 groups that one could make authentic midbrain dopamine cells of the type lost in PD from human stem cell sources. This work laid the foundation for a whole series of studies showing that these protocols could be adapted to the level needed for clinical trials (so called GMP) and that they not only worked reliably but could be manufactured in a relatively cheap and scalable fashion- two essential characteristics needed for commercial development. 


All of this has now meant that various companies and research groups are undertaking first in human trials in PwP with a variety of stem cell derived dopamine cells- including our own trial in Europe, celled Stem-PD that was funded from a grant from Novo Nordisk who are also hoping to develop their own stem cell therapy for PD. As such, there is now great excitement that this new generation of stem cell derived dopamine cell transplants will be safe and work in PwP and pave the way for a new approved approach for treating this condition with a one-off intervention.


 



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Andrew Cassy
Andrew Cassy
Apr 27

This podcast is encouraging in that we could be on the brink of another leap forward in clinical treatment option for many types of neurological conditions. Coming five years after this groundbreaking research conference on Development of dopaminegenic systems and stem cell circuits (DDSSCC 2019), which I was fortunate to attend as the patient ley representative.

https://rigeast.uk/decoding-our-biological-stew/ 

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