In the late 1980s and over the 1990s, researchers at Lund University in Sweden pioneered the transplantation of new nerve cells into the brains of patients with Parkinson’s disease. The outcomes proved for the first time that transplanted nerve cells can survive and function in the diseased human brain. Some patients showed marked improvement after the transplantation while others showed moderate or no relief of symptoms. A small number of patients suffered unwanted side-effects in the form of involuntary movements.
Ever since the first transplantations were carried out, a fundamental question has been whether the transplanted cells and their neural connections could survive and function over time despite ongoing disease in the patient’s brain. Now researchers at Lund University have proven that transplanted nerve cells can survive for many years and restore normal dopamine production in the transplanted part of the brain. The study has been published by the distinguished scientific journal Proceedings of the National Academy of Sciences (PNAS).
“Our findings show that transplanted nerve cells can survive and function for many years in the diseased human brain”, says Professor Olle Lindvall, one of the researchers behind the study. “This is the first time a patient has shown such a well-functioning transplant so many years after transplantation of nerve cells to the brain. At the same time, we have observed that the transplant’s positive effects on this patient gradually disappeared as the disease spread to more structures in the brain.”
The researchers followed a patient with Parkinson’s disease who underwent transplantation of dopamine-producing nerve cells 24 years before death. The patient showed such marked improvement that medication with L-dopa was no longer necessary three years after the transplantation. Brain-imaging technology allowed the researchers to show that dopamine function was completely normal in the transplanted brain structure ten years after the operation. The new study analyses the patient’s brain and the researchers can now prove that the transplanted dopamine-producing cells and their normal neural connections are still present almost a quarter of a century after the operation.
“This gives us a better understanding of how Parkinson’s disease spreads in the brain”, explains Professor Jia-Yi Li, who led the study together with Olle Lindvall and Anders Björklund.
“This study is completely unique”, says Professor Anders Björklund. “No transplanted Parkinson’s patient has ever been followed so closely and over such a long period. The patient was also unique in the sense that the nerve cells were only transplanted to one hemisphere of the brain, which meant that the other, which did not receive any transplant, could function as a control. What we have learnt from the study of this patient will be of great value for future attempts to transplant dopamine-producing nerve cells obtained from stem cells, a new development led by researchers in Lund.”
About this neurology research
Source: Cecilia Schubert – Lund University Image Source: The image is in the public domain. Original Research: Full open access research for “Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain” by Wen Li, Elisabet Englund, Håkan Widner, Bengt Mattsson, Danielle van Westen, Jimmy Lätt, Stig Rehncrona, Patrik Brundin, Anders Björklund, Olle Lindvall, and Jia-Yi Li in PNAS. Published online February 17 2016 doi:10.1073/pnas.1605245113
Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain
Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using 18F-fluorodopa and 11C-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson’s disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin- and α-synuclein–positive inclusions were seen, some with the appearance of typical Lewy bodies, in 11–12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.
“Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain” by Wen Li, Elisabet Englund, Håkan Widner, Bengt Mattsson, Danielle van Westen, Jimmy Lätt, Stig Rehncrona, Patrik Brundin, Anders Björklund, Olle Lindvall, and Jia-Yi Li in PNAS. Published online February 17 2016 doi:10.1073/pnas.1605245113