More MS news articles for June 2001

Human stem cell boost for Parkinson's disease

WCN 2001 - Day 3 - Wednesday 20 June 2001
Investigators: Ron McKay and Olle Lindvall
Wednesday Jun 20th, 2001
by Julie Clayton

Further optimism for the use of human stem cell transplants to treat neurological disorders came today with the revelation that human neural stem cells from fetal tissue can be triggered to expand in large numbers in vitro, before maturing into dopamine-releasing cells. Until now, these trials have had to rely on between two and four donor fetuses per patient to obtain enough cells. Now, a single fetus could provide enough material for one or more Parkinson's disease patients.

The availability of suitable donor tissue is a major scientific and ethical stumbling block in the progress of research into stem cell transplantation for Parkinson's disease. While scientists and ethicists are divided over the merits of continuing such trials, having larger numbers of cells could mean that more patients will benefit from this potential therapy.

Ron McKay, chief of the Laboratory of Molecular Biology at the U.S. National Institutes of Health in Bethesda, Maryland, reported the stem cell study to the World Federation of Neurology today.

McKay's team have isolated the neural stem cells from the ventro-medial cephalic region of fetal brains, at an earlier stage in development than those typically used for neural transplants into patients. Using growth factors the cells can be induced to divide. Upon withdrawal of the growth factors, the cells differentiate into dopamine-releasing neurons. The team have grafted these cells into rats, where they survive and continue to release dopamine. The work will shortly be published in the Journal of Neuroscience Research.

"This is an extremely promising technology ... but I think it will take years before we have something as good as fetal cells," declared Olle Lindvall, professor of Neurology at the University of Lund, Sweden. "The patient needs new cells that function in the same way as the cells that have died, and it is completely unknown, the extent to which [these stem cells] can function," he told BioMedNet News.

The numbers game is critical, according to Lindvall. It takes two to four donor fetuses to provide just 100,000 to 150,000 dopamine-releasing neurons - the minimum needed for a measurable clinical effect. But to increase cell survival and effectiveness of the transplant requires five or ten times this number for each patient, he said.

More than 300 Parkinson's disease patients worldwide have now received neural transplants, with only partial success. Far more work is needed to improve the effectiveness of the transplants for alleviating the full range of disease symptoms, says Lindvall.

The use of any type of stem cells in the clinic is still a long way off, he warned. "Any clinical application of a cell therapy must await convincing pre-clinical data showing not only functional efficacy but also biological mechanism," he told the audience of the same symposium.

Lindvall was delivering the Soriano lecture, and received the accompanying prize of US $1000 for his pioneering work in neural transplants for Parkinson's disease.

The next step for McKay will be to test how the human neural stem cells can be made to function in animal models of Parkinson's disease. Previous work showed that while fetal neural stem cells from mice could be driven to expand in vitro and release dopamine, they soon undergo a developmental switch to becoming GABA-releasing neurons instead.

While McKay and co-workers continue to investigate the signalling molecules responsible for this switch, they are also continuing with the alternative of using mouse embryonic stem cells instead of fetal tissue as a source of neural precursors. These have the advantage of almost limitless expansion in vitro before being made to mature into non-dividing neurons. They also offer more flexibility in the choice of final mature cells, says McKay.

Three years ago, McKay and colleagues reported driving embryonic stem cells to differentiate into more stable dopamine-releasing neurons that do not switch to GABA production. Now McKay claims he has unpublished data showing that these cells survive and function in animal models of Parkinson's disease.

Ultimately, the use of adult donors as stem cell sources would obviate the need for embryonic or fetal tissue, and so enable researchers to by-step the current ethical minefield of stem cell research. But no one has yet been able to drive the differentiation of adult derived stem cells into dopamine releasing neurons, according to McKay.

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