Protein Pump: Experimental therapy fights Parkinson’s

At first glance, people with Parkinson’s disease appear to have damaged muscles, as evidenced by tremors and rigidity. But in reality, their problem is a loss of brain cells needed to produce and regulate dopamine. Among its other duties, this compound enables the brain to send signals to muscles.

Scientists report in the May Nature Medicine that bathing the surviving dopamine-making neurons with a natural protein that induces nerve-fiber growth reverses some symptoms in Parkinson’s patients. The protein, called glial-cell-line-derived neurotrophic factor (GDNF), is plentiful in children but dwindles with age, tests in animals suggest.

Five patients, average age 54, received GDNF for up to 18 months. A group led by Steven S. Gill of the Institute of Neurosciences in Bristol, England, embedded two hockey-puck-size pumps loaded with GDNF under the skin of each patient’s abdomen. The pumps were refilled with GDNF by monthly injections.

The implanted devices sent a regular flow of GDNF up a tube to the person’s head and into the putamen. This brain region, central to movement, is starved for dopamine in Parkinson’s patients.

Within 3 months, movement had improved in all five patients. They had been unable to move at all during roughly one-fifth of each day before the treatment began, but that problem disappeared after 6 months of GDNF. Curiously, three patients who had previously lost their sense of smell recovered it after 6 weeks of GDNF, says coauthor Clive N. Svendsen of the Waisman Center at the University of Wisconsin–Madison.

He cautions that some of the gains could stem from a “placebo effect,” in which patients expecting to improve do so. However, brain scans of these patients at 6, 12, and 18 months after surgery to implant the pumps showed that dopamine supplies in the putamen improved over that time, Svendsen says. Patients suffered few side effects from the treatment.

Don M. Gash of the University of Kentucky in Lexington says this preliminary study of GDNF is encouraging. “If this lives up to its promise, it’ll be the first example of a [brain-cell-nourishing] factor being successful in clinical testing,” he says.

Studies in animals over the past 10 years have shown that GDNF can induce beleaguered dopamine neurons to sprout tendrils from axons, their natural extensions, Gash says. This sprouting increases the dopamine in the putamen, and the new tendrils boost the number of connections between neurons. These changes make signaling between brain and muscle cells more efficient.

The biotech company Amgen in Thousand Oaks, Calif., makes GDNF. The firm is currently conducting a similar trial with 32 Parkinson’s patients.

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