Taking part in the TransEuro trial

trials graphs etc smaller for webResearch is important to all of us. Taking part gives us the chance to feel that we are making a difference. One area of unfinished business is the potential for using cellular implants as a treatment for Parkinson’s. For the last three years I have been participating in the Transeuro research project, based at Addenbrooke’s hospital in Cambridge. As the third patient to receive an implant (out of thirteen that there will be in the UK altogether) this document describes my experiences and highlights the problems that still exist with this approach.

Background
Up until the first few years of the new century implanted cells were thought to be a potential ‘cure’ for Parkinson’s. In essence these are embryonic dopamine producing cells taken from recently terminated pregnancies. Clearly the use of human tissue in this way has the potential to be highly controversial and discussions around this topic undoubtedly delayed progress. The Transeuro project has the following aims:
• To identify the most appropriate methods for handling and storing fetal tissue.
• To identify those patients who are most likely to benefit from the treatment.
• To conduct operations and to learn from these.
• To demonstrate that some people with Parkinson’s can benefit from implants in the longer-term.

Transeuro is an ‘open label’ test – there is no sham surgery. The research institutes leading this work are Cambridge in the UK and Lund in Sweden. An initial sample of 150 was recruited. The intention right from the start was that this would provide sufficient sample to support the recruitment of two groups of 20 patients – half of these were controls, the other half test subjects. While the control sample were clearly aware that they were not receiving the treatment their role was to have PET scans every eighteen months to match those taken by the test group. The provision of long-term follow-ups was important as it was felt that this would enable placebo or other temporary effects to dissipate.

A number of research projects have been carried out, but there are still no definitive guidelines as to the preparation or the method of implanting cells in the brain. Then several studies actually showed negative results – people taking part in research were made worse. This finding, coupled with the arrival of George W Bush in the White House and the banning (on religious grounds) of federal funding to support this type of research, led to a moratorium on the use of surgical methods in the USA.
Set alongside this, however, was the fact that there were still, twenty years on, several patients in London who had received the operation and were now living virtually medication-free. The conclusion must be that there are some patients who will benefit.

Tablet with the diagnosis parkinson's disease on the display

My experience pre-operation
I found out in July 2014 that I had been selected as part of the ‘test’ group. I had always said that I was happy to be a subject in the research, but I did not want to be the first person to have the operation. I had my first operation in October 2015.

It may seem rather odd, but one of the first things I did (in September 2015) was to set up a blog. This was intended to outline my feelings at being selected and to give an overview of the project. There were several reasons for this – I circulated the URL to friends and family, most of whom had no knowledge of Parkinson’s or the research that was being carried out. In this sense the blog was intended to be educational. It also served as a way of letting people know where I was and what I was doing day by day. As time went by it became apparent that it would be some time before I would have the operation. The blog was perfect as people could look at the latest entries to find out what I was doing. Without this we may have been besieged by telephone calls from well-wishers.

While I wanted people to learn from my experience I was struck by the fact that more than 200 unique visitors came to the site in the first month. Most of those clearly looked around – the average page count was around five. The site won’t be pulled down anytime soon so there will still be opportunities to see everything that is there.

This part of the process was exacerbated by the difficulty in obtaining sufficient material for the implant – it takes a minimum of three aborted fetuses to provide enough material to treat one side of the brain. With only two feeder institutes in Cambridge and Cardiff it was often the case that three or four abortions might be available but one or two were unsuitable. Unfortunately this was not known until (at best) one or two days before the target date for the operation.

I eventually had the first operation on October 9th and the second on November 16th. In advance of the second operation there were numerous dates that had been set aside as potentials but these were closed down gradually on a week by week basis. Ultimately this proved to be the most challenging part of the research.

My experience post-operation 
As I write this at the beginning of December, 2015, I am aware that the post-op period is still only a few weeks old. That said, despite careful probing from the research team, I haven’t identified any particular problems. One of the requirements is to take immuno-suppression drugs for up to a year after surgery. Initially this caused me a problem because the steroids acted to reduce the effectiveness of my Parkinson’s medication, but this was sorted out by separating the doses of the two by at least an hour.

The second operation does not appear to have been as good as the first, the wound is deeper and will take longer to heal. The immediate recovery time from the operation was about the same.

I put together a mini FAQ that is on the website:

Q. Were you awake during the procedure.
A. You must be kidding me – this is a five hour operation!

Q. Might you need a third operation?
A. I hope not – my head only has two sides (left and right).

Q. Has it made any difference yet?
A. I can’t see any way that the required pathways could regenerate that quickly.

One of the benefits of being a test subject was the ‘celebrity’ status this conferred, with students being brought to see you on the ward and to ask questions. In one group the tutor asked me if I could remember what was said when I was given my diagnosis of Parkinson’s. I actually remember very well the conversation going something like this:

Consultant: “Did the GP give you any indication of what it might be?”
Me “No.”
Consultant: “I’m afraid it’s Parkinson’s Disease.”
Me: “That’s quite serious isn’t it?”
Consultant: “It’s an incurable brain disease”.

How many of you, he asked, can remember the detail of a conversation you had six years ago?

Next steps
There are alternatives to fetal tissue and this is where efforts are likely to be directed next. These come from two potential sources Induced Pluripotent Stem Cells (IPS) where the cells are taken from the host’s own body, re-programmed as dopamine-producing cells and inserted into the brain using similar methods to those outlined here. The advantage here is that cells from the respondent’s own body are used, thereby removing the need for ethics committees and making it much easier to obtain. The disadvantage is that there might be a very large number of applicants.

Another strand of thinking altogether is to use ‘growth factors,’ the best known of which is the glial cell-derived neurotropic factor (GDNF). Discovered in 1991 GDNF is a protein that has been shown to protect and restore many different cell-types. Alternatively, using combinations of these might also produce the best outcome.

Adapting these technologies is not straightforward, however, and further work will be required to develop the optimum solutions.

Richard Windle

This article appears in the current edition of On the Move. Richard also writes about this experiences living with Parkinson’s on his blog

Posted in PM Blog.