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Growth Factor Shows Promise In Parkinson's Patients

Date:
March 31, 2003
Source:
University Of Wisconsin-Madison
Summary:
By pumping a potent growth factor directly into the human brain, an international team of scientists and surgeons has demonstrated significant remediation of the debilitating symptoms of patients with Parkinson's disease.

MADISON - By pumping a potent growth factor directly into the human brain, an international team of scientists and surgeons has demonstrated significant remediation of the debilitating symptoms of patients with Parkinson's disease.

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The study, a phase 1 clinical trial designed primarily to assess the safety of administering a protein known as glial cell line-derived neurotrophic factor or GDNF, was reported today (March 31) in the journal Nature Medicine.

The study, according to co-author Clive Svendsen of the University of Wisconsin-Madison, induced a remarkable uptick in the motor skills of five Parkinson's patients in advanced stages of the disease, as well as the ability of their brains to store the neurotransmitter dopamine, a key chemical that helps the brain control muscles.

"Nobody's ever put a growth factor directly into the brain before," said Svendsen, a neuroscientist at UW-Madison's Waisman Center. "Our main concern was the safety issue, and it is important to keep in mind the limited scope of the trial, but the clinical results we observed were impressive."

The study was carried out at the Frenchay Hospital, Institute of Neurosciences, in Bristol, England. It was coordinated by neurosurgeon Steven S. Gill and neurologist Peter Heywood.

In the United States, Parkinson's afflicts about 1.5 million people. It is caused by the death of the brain cells that produce dopamine, the chemical messenger that helps control muscle movement. It is a chronic, progressive and ultimately fatal disease characterized by uncontrollable shaking and an inability of the brain to command muscles to move in a prescribed way.

The new study raises hope that GDNF, which has long been studied in rats and primates, may one day become a new therapy for alleviating the symptoms of Parkinson's patients.

"GDNF is known to protect dopamine neurons from cell death," Svendsen said. "We know from rat models that GDNF has strong positive effects on dopamine neurons. It can make them produce new processes and function better. It's like plant food. It makes cells healthier."

The protein was administered to the brains of the five patients through a catheter. Every day for 18 months, pumps pushed up to 40 micrograms of the protein into a region of the brain known as the putamen. There, it was absorbed by cells near the tip of the catheter and, Svendsen suspects, drawn deeper into the brain where the dopamine-producing cells reside.

The result was an improvement in clinical symptoms and daily quality of life of the patients.

"The tests that were done showed reductions in many of the rating scores for Parkinson's disease," the authors wrote. "This study warrants careful examination of GDNF as a treatment for Parkinson's disease."

After one year, patients exhibited no serious clinical side effects. The treatment also lessened the tremors caused by L-dopa, the drug most commonly used to treat the disease.

In assessing the drug's effect on patients, tests administered to measure motor skills showed a 39 percent improvement. Tests used to measure daily living activities showed a 61 percent improvement in patients given GDNF.

Underscoring improved muscle control, PET scans performed by David Brooks and Gary Hotton at London's Hammersmith Hospital showed a significant increase in the brain's ability to store dopamine, suggesting a direct effect of GDNF on the ability of dopamine to do its job of controlling the body's muscle movement.

"What we're seeing is that GDNF either upregulated dopamine metabolism, or it has inspired sprouting (of cells)," Svendsen said. "Either way, you've got more dopamine, which is good news."

Svendsen emphasized the limited scope of the trial and the fact that it was not a double-blind study. But he expressed confidence in the results and said they argue for a more comprehensive clinical trial with a larger number of patients. Such a trial is planned for the near future, he said.

"This is the first paper to show that a growth factor directly administered to the brain has any physiological effects on humans," said Svendsen.

The limitation of the approach in the study is that a pump and catheter are needed to administer the growth factor. But Svendsen added that the work advances the possibility of using genetically modified neural stem cells implanted in the brain to produce GDNF.

"It might be an ideal molecule. The key thing we know now is that it is safe."

In addition to Svendsen, Gill, Heywood, Brooks and Hotton, co-authors of the paper include Nikunj K. Patel, Karen O'Sullivan, Renee McCarter, and Martin Bunnage, all of Frenchay Hospital in Bristol.


Story Source:

The above story is based on materials provided by University Of Wisconsin-Madison. Note: Materials may be edited for content and length.


Cite This Page:

University Of Wisconsin-Madison. "Growth Factor Shows Promise In Parkinson's Patients." ScienceDaily. ScienceDaily, 31 March 2003. <www.sciencedaily.com/releases/2003/03/030331041137.htm>.
University Of Wisconsin-Madison. (2003, March 31). Growth Factor Shows Promise In Parkinson's Patients. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2003/03/030331041137.htm
University Of Wisconsin-Madison. "Growth Factor Shows Promise In Parkinson's Patients." ScienceDaily. www.sciencedaily.com/releases/2003/03/030331041137.htm (accessed November 28, 2014).

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