To boldly go

An article on the BBC news website has prompted me to write a post that I’ve been considering for a while. 

Billy Connolly, the edgy and flamboyant comedian, has been an outspoken supporter of research for a cure for Parkinson’s. He was diagnosed with the condition five years ago. This week he has publicised that he is willing to be a ‘guinea pig’ for a stem cell trial.

Irony, foreshadowing or mere coincidence?
Picture from http://bit.ly/SundayPost100

I have been asked about my 'stance' on stem cell treatments for Parkinson's in clinic, and I confess to not having a 'stance'. The reason for this is that the state of the science is truly in its infancy, certainly in terms of deliverables for people with Parkinson's. This is not to diminish the decades of work that have led us to where we are, but even heroic gestures, such as Connolly's will only inch us forward in the marathon that lies between now and the New Era of stem cell treatments.

In preparation for this blog post I have read an update from the recently established GForce-PD network: a network of researchers from around the world who are working together to bring stem cell treatment closer to reality. An excellent (technically written) history of the subject can be found in a Nature Reviews article written by Prof Roger Barker from Cambridge.

Landmarks in the history of stem cell treatment of Parkinson's.
From Nat. Rev. Neurol.doi:10.1038/nrneurol.2015.123

As a brief overview, stem cells can be derived from a 'matched-donor' - in a similar way to  how organ donation works currently; from embryos, which has both ethical and immunological issues; and from the individual themselves.

Different sources of stem cells
from https://doi.org/10.1016/j.stem.2017.09.014

They are then surgically implanted into the area of the brain that is most affected by Parkinson's, where they grow and develop into (hopefully) fully functioning dopamine-producing cells. In essence, the aim is not just to mask the symptoms like current treatments do, but return the individual's brain to how it would be functioning without Parkinson's.

I want to focus attention on one aspect of the discussions of this group as it has particular resonance with PREDICT-PD. There is a very difficult decision regarding whom to choose as participants in a trial of stem-cell treatment. Do you choose participants who've only recently been diagnosed, or do you choose people in later stages of the condition?

Some arguments for 'earlier' intervention is that these individuals will be physically fitter so at less risk of the initial surgery, and be better able to tolerate the immunosuppression required. They would also have longer to reap the benefits of their investment, and given that this kind of intervention would be at great financial cost to a health system, the payer (be that the NHS or any other health system) would get the best bang for its buck.

However, these arguments only hold water on the assumption that it works. The flip side of the coin also applies. A big fear of stem cell technology from the early days of the field, is that the new cells go outside the normal control systems of cells and develop into cancer cells. This might prove worse for someone that the slow progress of Parkinson's left untreated by stem cells. The immunosuppression also has long term risks, with unusual infections, or usual infections presenting in unusual ways. 

What about the other option? Individuals with more advanced disease have more physically measurable symptoms, and so less time is needed for a (very expensive) clinical trial to show differences between treated and untreated (or sham procedures). Given the risks outlined above, it could be conceived that stem cell treatment is a 'last-chance saloon' treatment that should be embarked on only where more established treatments have failed. We have written about the personal costs Parkinson's on this blog, and that as the condition advances the costs spiral. If stem cell treatment is withheld until later in the condition, there is a greater chance that the cost will be offset by savings in other areas, as the need for more help reduces with a return of independence in multiple areas.

There are no perfect answers. It is essential that a global effort is sustained to get us safely, ethically and rigorously through the choppy waters that lie between now and a time when stem-cell treatments are as commonplace as other treatments for Parkinson's.

RNR