For Bruce Wisnicki and other Parkinson’s patients, the benefit of most Parkinson’s medications might be summed up with the bromide: “This too shall pass.”
Because of the degenerative nature of the disease that depletes the dopamine producing brain cells, medications to control symptoms eventually lose their punch.
“I’m one of the lucky ones,” Wisnicki says. “I have the resources to have the finest care available.” And, he adds, he’s been able to participate in many clinical trials for drugs that help control his disease.
“Here’s the catch. I have been on these drugs for many years. Over time they become much less effective.” Even when he’s
doing well, Wisnicki, a 46-year-old Los Angeles resident, deals with the exaggerated, jerky movements that accompany the disease and its treatment.
“I spend half my day functioning and half my day trying to function,” he said. He was first diagnosed with Parkinson’s disease more than 10 years ago, when his two children were still toddlers.
“Parkinson’s is one of those diseases that teach us how much we really don’t know,” he said. “I hope you can find a cure so millions more people do not have to wait.”
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Curing Parkinson's Disease
Promise comes on little rat feet. Inky paw prints on a strip of paper show the short, tentative steps of a rat with a movement disorder caused by Parkinson’s-like brain injury. A second strip shows the long stride of a Parkinson’s model rat injected with stem cells that tamp down activity in a part of the brain overactive in Parkinson’s. This study with rat fetal stem cells points the way toward treatments for a disease which affects 1 in 100 people older than 60.
“Parkinson’s disease is really an ideal target for cell-replacement therapy, specifically because a particular cell type is lost and could be replaced,” said Arnold Kriegstein, MD, PhD, and director of the University of California, San Francisco, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research.
Parkinson’s is a movement disorder characterized by the loss of neurons that make the chemical dopamine. When all works properly, the dopamine neurons extend from the midbrain to areas that control movement, including the striatum and the basal ganglia. As dopamine neurons die, the brain loses dopamine’s modulating effects. Tremors develop. Movement slows and becomes difficult to initiate. Muscles stiffen. Facial expression diminishes.
Researchers learned a great deal from work in the 1980s and ’90s in which fetal dopamine cells were transplanted into the brains of Parkinson’s patients. While the transplants had only limited success, the studies proved that transplanted cells would produce dopamine, said Jeff Bronstein, MD, PhD, director of the Movement Disorders Program at the University of California, Los Angeles.
There’s reason to think that the special characteristics of stem cells will bridge the shortcomings of fetal cells, Kriegstein said. For instance, there often weren’t enough fetal cells available to make a significant difference in transplants. “With stem cells the promise is we can make an unlimited number of cells.”
Fetal cells didn’t move beyond the site of injection and didn’t integrate well with surrounding tissue. “There’s evidence that embryonic stem cells will actually integrate much better,” he said.
Although many laboratories hope to replace dopamine-producing stem cells, Kriegstein’s animal experiments instead transplant inhibitory neural stem cells to ameliorate the effect of missing dopamine. Once injected into the rodent brain, “They migrate. They form synapses. They sprout axons that actually contact the host neurons and they function as inhibitory neurons,” he said. “And in behavioral tests, they actually improved motor function of these Parkinsonian rodents.”