Transplanted Dopamine Cells Show Promise for Treating PARKINSON’S DISEASE
The big news this week was the story in Cell Reports; they transplanted dopamine cells that remained healthy and survived for 14 years. The research team, headed by Ole Isacson, M.D., from McLean Hospital and Harvard University in Boston, MA, found that they also improved the function of dopamine transporters (DAT) and mitochondria. Dopamine transporters are specialized proteins that carry the neurotransmitter dopamine. The researchers examined the brains of five subjects, all of whom had received injections of fetal cells when they were already in late stages of PARKINSON’S DISEASE. These subjects had died from causes other than PARKINSON’S and had given permission for their brains to be examined post mortem.
Fetal cell transplantation into the brains of people with PARKINSON’S DISEASE has a controversial history. Transplanted cells have previously been shown to follow the same path of deterioration that occurs in the subjects’ own cells. Transplanted cells also have been shown to develop Lewy bodies, the abnormal small inclusions of alpha-synuclein associated with the dementia sometimes seen in PARKINSON’S DISEASE. For these reasons, cell transplant therapy for PARKINSON’S DISEASE has been rather controversial. Additionally, the cells utilized in this currently reported study were derived from aborted fetuses, albeit with maternal approval for their use in research, but still a significant ethical issue in the United States, This study was performed 14 years ago in Canada. According to Dr. Isacson, only about 25 people have received this particular method of cell transplantation in the last two decades.
In this study, the researchers sought to understand the long-term interactions on the transplanted cells including the aging process. They specifically examined the dopamine transport (DAT) system and mitochondrial function as a means of neuronal expression. They examined both the transplanted cells and the dopamine producing cells of the patient’s own brain. The transplanted cells had remained healthy and free of the disease process, while the patient’s own cells showed the marked progression of the disease. Previous studies by other investigators have not shown the same results. Dr. Isacson suggests that perhaps it is the method of transplantation that improves the outcome.
Cell replacement therapy for PARKINSON’S DISEASE has the potential to provide better therapeutic treatment by replacing diseased and damaged neurons with healthy and functioning new ones. But there is as yet much that is not known about either the disease process itself or how transplanted cells can successfully graft into diseased tissue and restore function. Some studies using fetal cells have shown the transplanted cells do provide limited therapeutic benefit, alleviating some of the symptoms, however, the disease continues to progress, the cells were not a cure. Obtaining sufficient cells from aborted fetuses is also an ethical dilemma. Dopamine producing cells laboratory grown from embryonic stem cells also have a less than perfect record, while some recipients have benefited, others have seen the cells multiply to form tumors. Other attempts to grow stem cells from fibroblasts found in skin or from bone marrow have shown only limited success. More basic research is needed to understand both the genetics and biological processes involved for cell replacement.
Hallett et al., Long-Term Health of Dopaminergic Neuron Transplants in Parkinson’s Disease Patients, Cell Reports (2014), http://dx.doi.org/10.1016/j.celrep.2014.05.027 (article in press)
Review by Marcia McCall