From rxpgnews.com
Parkinson’s Approach With Stem Cells A Promising First Step
By University of Rochester Medical Center,
Dec 4, 2006 - 11:03:44 AM
Brain cells derived from human embryonic stem cells improved the condition of rats with Parkinson’s-like symptoms dramatically, but the treatment caused a significant problem – the appearance of brain tumors – that scientists are now working to solve.
The work was reported by neurologist Steven Goldman, M.D., Ph.D., professor of Neurology at the University of Rochester Medical Center and chief of its Division of Cell and Gene Therapy, and Neeta Roy, Ph.D., assistant professor of Neurology at Cornell’s Weill Medical College.
“The results are a real cause for optimism,” said Goldman. “These animals with severe Parkinson’s symptoms had a dramatically improved outcome after treatment. Now we have a new problem to work on, how to achieve the same benefit without creating tumors. But we expect to be able to solve this problem within the next year or two, using new approaches to cell sorting that we’ve been developing.”
“All in all, this is the way medical discoveries move forward: One step at a time.”
Goldman has spent much of his career creating ways to isolate stem cells, discovering the molecular signals that help determine what specific types of cells they become, and then re-creating those signals to direct the cells’ development. It’s the versatility of stem cells that make them so attractive. If scientists like Goldman are successful directing their development, such cells could provide a ready source of cells custom made to treat a given disease – for instance, myelin-producing cells for multiple sclerosis, or the specific types of cells that die in patients with Parkinson’s or Huntington’s diseases.
In the experiment reported in Nature Medicine, Goldman, Roy and colleagues set out to grow brain cells called neurons that produce dopamine, a crucial brain chemical lacking in patients with Parkinson’s. They began by isolating human embryonic stem cells, then using genes such as “sonic hedgehog” and fibroblast growth factor 8 that make chemicals in the normal brain environment. Such signals are the body’s natural way of directing stem cells to develop into the specific cells needed.
Past attempts at using stems cells to make this type of neuron had achieved modest success, but only relatively small numbers could be produced in tissue culture. To improve upon this, Roy and Goldman attempted to re-create the natural environment of the developing brain as much as possible, so it would seem to the stem cells that they were developing in the part of the brain where dopamine neurons are normally made. The team did so by raising the cells together with brain cells known as astrocytes, which had come from the same brain region. These cells have long been known to play a crucial role nourishing neurons.
The result was that more than two-thirds of the stem cells developed into precisely the type of cell needed to treat Parkinson’s disease – dopamine-producing neurons. That percentage is far higher than any previous experiment had achieved.
The team then injected the cells into the brains of rats with Parkinson’s-like symptoms, and watched for 10 weeks. While rats with the disorder walked in circles when prompted to move, as if they were chasing their tails, rats transplanted with the new cells recovered normal function and eventually stopped walking in circles. By eight weeks after treatment, the tail-chasing behavior ended completely, and they were walking and running normally.
Yet when the brains of the animals were examined, the team found tumors within the brain grafts. Goldman said the tumors sprang from stem cells that had started on the road to becoming neurons, but then stalled in their development and grew out of control. The team is working on ways to filter out those cells, to reap the benefits while avoiding the side effects of the approach.
“The appearance of tumors was disappointing, but not surprising,” said Goldman. “The goals of this experiment were to create a population of cells that had many more dopamine neurons than previous attempts yielded, and to measure whether a group of cells with so many of these neurons would yield real-life benefits in terms of behavior. We accomplished both tasks. The cells improved the disease symptoms dramatically, beyond what we expected.
“In this first attempt of the technology, we did not attempt to try to absolutely purify the cell population that was transplanted – thus the brain tumors. The experiment confirmed that we need to have an absolutely pure cell population, and we are working on ways to do that.”
The work was supported by the National Institute of Neurological Disorders and Stroke, and the Michael J. Fox Foundation. Other authors of the paper, all at Cornell, are Carine Cleren, Shashi Singh, Lichuan Yang, and M. Flint Beal.
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