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Parkinson's Treatment With Pluripotent Stem Cell-Derived Neurons Shows Promise

Monday July 01, 2013

Christian Nordqvist

Medical News Today - In an animal experiment using primates modeled with Parkinson's disease, transplanting human embryonic stem cells revealed "robust survival" of the cells after six weeks. The researchers, from Yale University, Rush University, the St. Kitts Biomedical Research Foundation and the University of Colorado added that the cells were "well integrated" into the host animals.

The study - "Survival and Integration of Neurons Derived from Human Embryonic Stem Cells in MPTP Lesioned Primates" - has been published in the journal Cell Transplantation.

Dr. D. Eugene Redmond, Yale University School of Medicine, said "Parkinson's disease was one of the first neurological disorders to be studied for potential replacement of lost neurons. Since the 1970s there has been significant progress with learning the required gene expression, growth factors and culture conditions for differentiating cells into apparent dopamine neurons."

However, the authors explained that there have been disappointing results when transplanting dopamine neurons into rodents or monkeys - they did not become long-lasting midbrain specific neurons. They added that "there have only been pilot reports of functional improvement".

In this study, the scientists assessed the long-term survival of apparent dopamine neurons in monkeys modeled with Parkinson's-like symptoms. They also tested the functional benefit of the new neurons.

The authors found, as in previous studies, that gene expression of TH (tyrosine hydroxylase) was "transient" after transplantation. TH is a synthetic enzyme that limits dopamine production. They realized that they needed to determine when the optimal cell stage was, as well as the ideal culture environment for optimum graft survival, and also other factors that might influence the outcomes of cell transplantation.

The authors reported that there was better cell survival when a more robust immunosuppression regime was employed, compared to those used in previous primate studies.

The researchers wrote:

"Our results demonstrate that pluripotent stem cell line-derived neurons retain the capacity to robustly survive and respond to cues in the primate brain. The absence of TH expression indicates that other methods may be necessary to produce and maintain the proper midbrain dopaminergic form of the cells in vivo."

Even though this study showed that cells can survive, the authors emphasized that longer-term studies are needed to determine what factors might have an effect on long-term function replacement and whether they demonstrate considerable reversal of parkinsonism, the formation of tumors and dyskinesias. Dyskinesia refers to involuntary movements; a common side effect of Parkinson's treatments used today.

Stem cell study may help to reveal how a genetic mutation leads to Parkinson's symptoms - scientists from the Salk Institute for Biological Studies managed to reprogram skin cells from Parkinson's disease patients with a known genetic mutation in order to identify damage to neural stem cells which play a key role in the development of the disease. They reported their findings in the journal Nature (October 2012 issue).

The authors believe their findings may pave the way to new ways to diagnose and treat Parkinson's.

Team leader, Juan Carlos Izpisua Belmonte explained that the team found a common mutation to a gene that produces LRRK2, an enzyme responsible for both sporadic and familial cases of Parkinson's, which deforms the membrane of the nucleus of neural stem cells. If the nucleus is damaged it can lead to the cell's destruction, as well as reducing its ability to produce functional neurons, including those that respond to dopamine.

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