A postmortem examination of a patient with Parkinson's disease (PD) who underwent dopaminergic cell transplantation 24 years ago has shown that the transplanted neurons survived and had reinnervated the brain for all that time. 

Although feotal cell transplantation fell out of favor in the 1990s after trials in the United States showed side-effect issues, including severe dyskinesias, different techniques for transplantation which were more successful than the US trials continued to be developed and research in this exciting area of PD treatment is now progressing well. These recent findings provide encouraging "proof of concept" that cell transplantation may be a viable option for patients with PD, the researchers, from Lund University, Sweden, say.

In a paper published online in Proceedings of the National Academy of Sciences of the United States of America on May 2, the researchers report that the patient experienced major clinical benefits for at least a decade after transplantation.

The patient showed such marked improvement that medication with L-dopa was no longer necessary 3 years after the transplantation, they note. Imaging indicated that dopamine function was completely normal in the transplanted brain structure 10 years after the operation, and the latest postmortem findings show that the transplanted dopamine-producing cells and their normal neural connections are still present almost a quarter of a century after the operation.

However, the improvements in symptoms were gradually lost from 14 years after transplantation, "indicating that even extensive graft-derived dopaminergic reinnervation loses its efficacy in a severely degenerating brain," the researchers state.

This patient represents the longest survivor at 24 years posttransplant, and we show that even at this long after the procedure the transplanted cells have completely reinnervated the putamen

Lead author, Professor Jia-Yi Li

Because patients received the transplant on only one side of the brain, the researchers could compare the two sides of the brain on postmortem examination. "We found the transplanted side showed complete reinnervation whereas the nontransplanted side showed no dopaminergic profile." 

Professor Li noted that the more than 10 years of symptom relief "is a very good result from one single procedure." He added: "But the eventual gradual return of symptoms shows that the degeneration of the brain does not occur just in the putamen — it spreads throughout the brain." The patient also developed cognitive impairment at around the 14-year mark, and progressive dementia ensued.

"This Lewy body pathology is associated with Parkinson's dementia, which only develops in certain patients," he added. "Our results indicate that the Lewy body pathology propagates from the host brain into the transplanted cells."

New European Trial Underway

Following the feotal cell transplantation work in the 1990's, preclinical work continued to refine the techniques involved, and a new European clinical trial of feotal cell transplantation for Parkinson's is now underway.

Commenting on this case report for Medscape Medical News, James C. Beck, PhD, vice president, scientific affairs, Parkinson's Disease Foundation, agreed that the findings would be useful to guide future research.

"What is notable about this case is that it gives us an idea of what we could expect from a successful transplant," he said.

Dr Beck said that while techniques may have now improved, feotal tissue transplant might be a possibility for a few selected patients, "but it is not going to be widescale treatment routinely available because there will be a limited supply of feotal tissue and the whole issue of using feotal tissue is ethically very difficult."

Stem cell therapy is much more viable as stem cells can be produced in large quantities in a standardised procedure, and clinical trials of stem cells in Parkinson's are expected to start soon. 

Roger Barker, MBBS, consultant neurologist at Addenbrookes Hospital, Cambridge, who is coordinating the new 'Transeuro' trial of feotal cell transplants funded by The Cure Parkinson's Trust (CPT), said the report was "very interesting and important in that it shows that grafted dopamine cells can survive for so long in the brain of a Parkinson's disease patient."

But he agreed that this field will move toward stem cells in future for ethical and logistical reasons. Stem cells are an important area of transplant research CPT is also funding.

Professor Roger Barker spoke about his research projects at CPT's recent research update meeting - see Professor Barker and other key speakers at the research meeting.

This article was compiled using excerpts taken from Medscape Medical News 'Parkinson's Cell Transplant Shows Good Reinnervation at 24 Years' written by Sue Mason and published May 10th 2016

Read the Full Published Paper.