www.nature.com/news/2006/061016/full/061016-16.html
Kerri Smith A rat's movement troubles can be almost completely cured with transplants of fresh neurons. Alamy The symptoms of Parkinson's disease have been relieved in rats using a stem-cell treatment. But a potentially cancerous side effect might put the brakes on such therapies for humans. Parkinson's disease kills off neurons that produce the neurotransmitter dopamine, leading to problems with movement and balance. Most treatments currently involve replenishing the dopamine through drugs. But researchers are keen to develop longer-term solutions, using embryonic stem cells to make replacement dopamine neurons. But it has so far proved difficult to produce enough of the right kind of cell; there are several types of dopamine neuron, and only some of them will do the job. "Not all dopamine neurons are created equal," says Steve Goldman of Cornell University Medical College, New York, who leads the study.
Grow your own Goldman and his team took human fetal midbrain tissues, in which dopamine cells are made, and extracted glial cells, whose normal role is to support and maintain the growth of neurons. They then cultured stem cells in this glia-rich environment. "What we were really trying to do was to mimic the environment of the developing brain to increase the efficiency of dopamine-neuron generation, but also to bias the cells towards generating the type of dopamine neurons that we wanted," says Goldman. When the new dopamine neurons were transplanted into the brains of rats with the symptoms of Parkinson's disease, the animals recovered almost entirely. "The positive results were really remarkably strong," Goldman says. "The animals exhibited almost a complete restoration of normal function." Each stem-cell transplant also contained cells that had failed to become neurons, and which remained undifferentiated. These cells keep dividing, and can turn into tumours, says Goldman. To avoid it, the cells will need to be sorted and the differentiated ones isolated, says Olle Lindvall, a neurologist at University Hospital in Lund, Sweden. It will be several years before clinical trials of stem-cell approaches to Parkinson's disease can proceed, says Lindvall.
In the meantime, others are working on using gene therapy to stimulate neurons already present in the brain to produce more dopamine. This week, an American biotechnology company called Neurologix reported successful, preliminary trials of this technique. They introduced a harmless virus, equipped with a gene involved in the dopamine system, into the brains of patients. All showed an improvement of at least 25% in their symptoms. But gene therapy too comes with a host of problems, including learning how to properly regulate the new genes, and the improvement isn't as dramatic as seen with the stem-cell approach. "Neither gene therapy nor stem cells are ready for primetime," he says.
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