Transplantation for Parkinson’s disease:
Don’t count it out yet
During the past decade there has been one area where early diagnosis will certainly make a difference: neural transplantation.
This week’s Nature drew attention to an article from Ole Isacson’s lab at Harvard. The article appeared in the high-impact journal Cell Stem Cell and is entitled “Successful Function of Autologous iPSC-Derived Dopamine Neurons following Transplantation in a Non-Human Primate Model of Parkinson’s Disease”(1). This represents a significant step towards a potential treatment or even a cure for PD. In the Maritimes, we have heard very little about transplantation of dopamine neurons since the departure of Dr. Ivar Mendez, so it is worth reviewing the current situation.
Neural transplantation for PD was started in the mid-1980s, flourished from 1990 to 2002, and collapsed in 2002-2003 It is interesting to note that during the years 2003-2009, centres that were not part of the NIH studies found that transplants provided significant improvements in PD symptoms with few dyskinesias. This led to a call to continue neural transplantation (2) and to the €12 million Transeuro project currently underway in the UK and Sweden www.transeuro.org.uk/. It turned out that the two NIH studies were seriously flawed but, by the time that was realized, Parkinson’s disease research had moved on to GDNF (which also failed, but that is another story) and other treatments.
But back to the Hallett paper (1). One of the dreams we had in the early days of neural transplantation work was the idea of either stimulating dopamine neuron production in patients or developing ways of taking the patient’s own cells, changing them into dopamine neurons and implanting the cells back into the patient. Since it is the patient’s own cells, immunosuppression would not be necessary. The advent of iPSC technologies also meant that we would no longer be handicapped because of the supply of tissue. The Cell Stem Cell paper by Hallett et al (1) studied monkeys that had been treated with MPTP to produce PD. They then took skin fibroblasts from individual monkeys and treated them with the factors necessary to convert cells to dopamine neurons. The cells were then transplanted back into the monkeys from which they were derived. The cells survived without immune suppression, re-innervated the putamen and improved motor function.
What does this all mean? Currently there are only symptomatic treatments fo r PD so there is a huge unmet medical need for a treatment to halt progression. iPSC-based treatments are a matter of a few years away; I predict that clinical trials will begin in late 2015-early 2016. When and where will these trials be held? That remains to be seen.
1. Hallett, P.J., Deleidi, M., Astradsson, A., Smith, G.A., Cooper, O., Osborn, T.M., Sundberg, M., Moore, M.A., Perez-Torres, E., Brownell, A.L., et al. (2015). Successful Function of Autologous iPSC-Derived Dopamine Neurons following Transplantation in a Non-Human Primate Model of Parkinson’s Disease. Cell Stem Cell.
2. Barker, R.A., Barrett, J., Mason, S.L., and Bjorklund, A. (2013). Fetal dopaminergic transplantation trials and the future of neural grafting in Parkinson’s disease. The Lancet Neurology 12, 84-91.