Thursday July 1 2010
Parkinson's is cause by a lack of dopamine in the brain
Foetal transplants for Parkinson's disease patients have been “brought closer to reality” by new research, said The Independent today.
Trials of the experimental technique, which implants tissue from foetuses into the brain, had been stopped in the 1990’s after many patients experienced uncontrollable jerky movements known as dyskinesias. This new research was a follow-up study of two patients who had experienced the side effect after being treated with neural transplants some 15 years ago. Its findings suggest that dyskinesias may be due to imbalances in neurotransmitters following the transplants, and that these may be treatable with drugs.
Although this study only looked at two patients, the ability to control the dyskinesias that led to earlier trials being halted is a potentially exciting prospect in the fight against Parkinson’s disease.
Where did the story come from?
The study was carried out by researchers from Imperial College London, University College London, and Lund University and Neuroscience Centre in Sweden, where some of the original tissue transplants took place. The study was supported by the UK Medical Research Council and the Swedish Research Council.
One author is supported by a research grant from the Michael J Fox Foundation for Parkinson’s Research. The study was published in the peer-reviewed journal, Science Translational Medicine.
The Daily Mail also covered this research and like The Independent focused on the hope it may offer people affected by this devastating disease. The opposition expected from anti-abortion groups is referred to through a quote from the Pro-life Alliance.
It is worth noting that while ethical concerns over this treatment must have been resolved in the 1980’s for the procedure to have been trialled in the first place, new trials using this technique will need to get new ethical approval from the relevant scientific and legal bodies of each country involved.
What kind of research was this?
Parkinson's disease is the result of having too little of the chemical dopamine (a neurotransmitter) in the parts of the brain that control movement. There are other neurotransmitters, particularly serotonin, that are involved in movement and an understanding of the balance of these is an important part of current research into normal and diseased brain function.
The trials in the 1990s assessed the effects of transplanting foetal brain tissue into the brains of people with Parkinson’s disease with the aim of relieving symptoms. This research examined the role of a specific type of neuron (brain cell) within the transplanted tissue used in these original trials.
The original research was halted because some participants developed uncontrollable movements and jerking of limbs, known as dyskinesias. These were of a different type to the involuntary movements expected from Parkinson’s or Parkinson’s treatments. The researchers wanted to further investigate why dyskinesias occurred in about 15% of the patients treated with foetal neural transplant.
The researchers used a range of techniques, including clinical evaluation on multiple occasions, a PET tissue-imaging scan and a MRI scan of radioactive marker chemicals introduced to the brain to highlight areas of neural activity. These advanced techniques were used on two male patients who had received the neural transplants in the 1990’s.
The researchers also tested the patients’ responses to a medication in an attempt to identify the cause of their troublesome dyskinesias. To do this they compared the symptoms the men experienced when given a drug to suppress neurotransmitter secretion and to the symptoms seen when the two men took a placebo.
This complex research appears to have been conducted well and was reported in an understandable way.
What did the research involve?
The aim of this research was to examine the role of serotonin-related neurons in the development of graft-induced dyskinesias in two patients with Parkinson’s disease who had been treated with a foetal neural transplant in the 1990’s. Both patients had shown recovery of movement after their transplantation, which was done in Sweden, but had developed dyskinesias along with some of the other 24 participants of the early trial.
During the 1980's and 90’s, researchers transplanted dopamine-producing nerve cells taken from foetuses after a routine termination of a pregnancy. The nerve tissue was injected into specific parts of the patients’ brains that were lacking in dopamine, and any rejection of the tissue was controlled with immunosuppressive treatments. Many patients recovered significantly, although some went on to suffer involuntary muscle spasms.
Two male patients aged 65 and 66 years were selected from those that were still alive.
The researchers used two imaging techniques, a PET scan superimposed on a MRI scan, to show the areas of the brain that showed serotonin activity. They also scored the two patients for dyskinesias using a recognised scale and then tested them for up to four hours after they were given a drug buspirone. Buspirone is a ‘serotonin agonist’ compound that activates serotonin 1A receptors, mimicking the effect of the neurotransmitter serotonin. The researchers present their data comparing a placebo and no treatment.
What were the basic results?
The researchers showed from the live imaging techniques that both patients had excessive serotonin nerves in the transplanted areas of the brain. Both patients had also shown major improvements in their disease following transplantation and had recovered some dopamine production.
The jerky movements, dyskinesias, were reduced for three to four hours after they were given the drug buspirone, which dampens the patient’s own release of serotonin. This, the researchers say, also indicates that the dyskinesias were caused by too many serotonin-producing neurons.
How did the researchers interpret the results?
The researchers say that their observations suggest ‘strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson’s disease with fetal tissue or stem cells’.
They list three potential strategies:
- they could dissect out the serotonin-producing parts of the graft tissue before transplant
- they could check that storage techniques were not responsible for the change in balance between serotonin and dopamine production in the transplanted tissue.
- they also propose that the serotonin neurons could be kept to a minimum or removed completely by cell sorting
If, however, the same side effects still develop in future neural transplantation trials despite these strategies, the researchers now know they can be effectively treated with a serotonin agonist
This interesting research was only conducted on two patients but has important implications for the treatment of this devastating disease. It is important to take into account a few features of the research that affect how rapidly the technique might be approved for use again.
- Few patients who have had neural transplants in the UK could be studied. Of the five patients who recieved transplants in the UK, two had died and one was bedridden and unable to participate in the research. More patients are needed if longer-term effects, adverse events and safety of any revised technique are to be tested in new trails.
- The drug tested, buspirone, was given by injection and lasted about three to four hours. This may limit the ability to use this therapy in routine treatment after a transplant.
- Both patients were originally treated 10 to 20 years ago and the severity of their disease and potential differences in available techniques used will not necessarily be applicable to all patients.
While this is clearly still an experimental therapy it does seem that refinement of techniques in a research setting could lead to benefits for selected patients in time.