Here is the approved account of the presentation:
Research Meeting – Newark branch - 17th February 2014
Dr Roger Barker, Department of Clinical Neurosciences, University of Cambridge
The Future Treatment of Parkinson's disease
An amazing 90 people turned up to hear Dr Roger Barker speak on this topic and were not disappointed. His was an exceptionally clear account of several lines of potential therapy for Parkinson's disease. But it was necessary to start with some basic facts about the nature of the disease and also why it is important to recognise that not all Parkinson's is the same.
We all know that everyone's Parkinson's disease is different. But a study of all the new cases arising in Cambridgeshire over recent years has revealed that, from the point of view of the neurologist, there are broadly two types that call for two different types of treatment. Characteristic of the first type is an age of diagnosis over 72 years coupled with early cognitive problems. It is a sad but common observation that people in this category tend swiftly to develop a range of symptoms, both mental and physical, that go beyond the characteristic Parkinson's ones of tremor, stiffness and slowness of movement.
The second type, predominantly with younger onset, has the characteristic motor symptoms of Parkinson's but they tend to remain relatively stable for perhaps many years.
It is only part of the story to say that Parkinson's is due to the dopamine-producing part of the brain. Other parts of the nervous system are also affected and this is particularly the case for patients of the first type. For the second type, replacement of dopamine in one way or another can be very effective. But for the first type, dopamine drugs do not adequately address symptoms like dementia, walking problems, hallucinations and so forth; they become increasingly troublesome even after tremor and stiffness are reduced by the most carefully tuned dopamine-replacement therapy.
Dr Barker described a number of trials involving the transplantation of foetal neural cells to replace the dopamine cells lost. Some patients experienced great improvement, occasionally being able to come off medication altogether. Others, however, developed severe dyskinesia. Another set of trials, however, led to the conclusion that the transplants were no more effective on average than sham transplant operations on patients. Yet the TRANSEURO group led by Dr Barker decided to persist in this line of research because, first, certain individuals clearly benefited from transplants and, second, there were several possible reasons why the trials gave negative results one being that patients who were most likely to display negative outcomes – ie the patients of the first type described above - were not filtered out beforehand. New trials starting March 2014 will pay particular attention to (i) better patient selection, (ii) optimised collection of foetal cells and (iii) optimised delivery of the cells to the brain.
Foetal cell transplantation is expected to produce proof of principle but is unlikely to become widely practised. This is because the development of neural stem cells is expected to mature over the next decade and there are good reasons why these should be used instead.
Dr Barker also described a couple of other potential treatments which, again, would be of greater benefit for patients of the second type where dopamine replacement therapy is effective at restoring quality of life.
The first is a gene therapy named Prosavin which introduces a gene into the brain which produces dopamine where it is needed.
The second is the use of a chemical substance called GDNF – glial cell derived neurotrophic factor. Hopes are – with some believable evidence – that GDNF is able to restore damaged brain when it is infused into that part where dopamine cells have been lost. Quite a complicated story surrounds GDNF research which, again, involves initial promising results being overtaken by negative ones. Yet, again, some sustainable reasons have emerged that could explain the failures and a new trials have been started by Stephen Gill's team in Bristol.
So for the people with Parkinson's of the second type for whom dopamine replacement therapy works pretty well there are plenty of hopeful developments. But there are other lines of investigation that could help those patients of type one where what is needed is something to slow down or stop the progress of the disease in all the different parts of the nervous system where the pathology exists.
Dr Barker explained that around fifteen years ago it was discovered a particular ubiquitous protein called alpha-synucein was at the heart of the disease because its molecules can misfold and eventually aggregate together to form the major part of the insoluble bodies in nerve cells discovered many years ago by Lewy in Parkinson's patients. Research over only the last few years has shown that (a) this misfolded protein is found in many parts of the nervous system outside of the brain and (b) seems to appear first in the nerves of the gut and the olfactory bulb. Not only that but it spreads along the nerves in a way reminiscent of prion disease where a missfolded protein molecule can act as a template for other normal protein molecules to induce them to misfold too. This is why it is said that you probably had Parkinson's for ten years before it was diagnosed because it could be that it takes that long to reach the dopamine-producing cells and destroy half of them to produce the characteristic Parkinson's symptoms.
So maybe the pathology of Parkinson's is kicked off in the gut by an ingested toxin. This has brought researchers round to thinking about whether there is a way of removing the misfolded alpha-synuclein to stop the prion-like chain reaction so that it can do no more damage. Work is now going on to see whether anti-bodies can be developed. Maybe in future there will be a vaccination against Parkinson's particularly for those at especial risk.
As you can guess, Dr Barker spoke in fascinating detail only the bare bones of which are recorded here. There is little wonder about why he is in demand as speaker. He spoke at the World Parkinson's Congress in Montreal and covered a lot lot of the same material as at Newark. The video recording has now been put up on the web and you can view it, with all the slides, at http://www.icastpro.ca/events/wpc/2013/10/04/3rd-world-parkinson-congress/play/1694 (You may have to register but it is free.)
