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Gene Therapy For Parkinson's Hitches Ride On Virus

OHSU is one of nine sites studying whether CERE-120 reduces symptoms of disorder .

A new clinical trial at Oregon Health & Science University is examining whether therapeutic genes that hitch a ride with a harmless virus attracted to nerve cells can reduce Parkinson's disease symptoms.

The year-long trial at OHSU and nine other sites around the country involves pairing an inactive virus known as AAV2 with a gene that causes nerve cells to produce neurturin, a protein that may improve the function of dopamine-producing cells and protect them against damage.

Parkinson's disease is caused by a deficiency of nerve cells that produce dopamine and is associated with such symptoms as tremor, muscular stiffness and slowness of movement.

Previous studies have shown that laboratory animals given the gene produce neurturin for at least a year, with no decline in expression, said lead investigator John "Jay" Nutt, M.D., professor of neurology in the OHSU School of Medicine and director of the OHSU Parkinson Center of Oregon.

"It looks like it's permanent once you get it in there," he said. "We think the neurturin will coax (nerve cells) back into full functioning."

AAV2-NTN is considered harmless in humans because genes that allow it to replicate have been removed. "This is a virus that's not known to cause any human diseases," Nutt explained. "It's a virus that almost exclusively goes into neurons, so it targets neurons."

The study drug containing the gene-virus duo, or "gene transfer agent," is called CERE-120. It was developed and is manufactured by San Diego-based Ceregene Inc., which also is funding the multicenter trial.

The drug is administered during a surgical procedure in which injections are made directly into the putamen, the part of the brain where dopamine nerve terminals are deteriorating because of Parkinson’s disease. Eight injections are made - four on each side of the brain - at different elevations to assure all of the putamen is covered with the agent.

Fifty-one people are being recruited for the study, including four to eight participants at OHSU. They will be assigned to one of two groups: One that receives treatment with the study drug; and one that will have a surgical procedure meant to simulate that used to give the study drug, but without the drug.

Two-thirds of the study group will receive the study drug. If results confirm the continued safety and effectiveness of the study drug following the conclusion of the trial, another study will be opened to allow subjects who received the placebo surgery to be treated with CERE-120. Participation will be made available to all subjects deemed suitable for the surgical procedure by the participant’s doctor.

Nutt cautioned that CERE-120 isn't a miracle drug that restores nerve cells destroyed by Parkinson's disease.

"This is not going to be something where (participants) wake up after the operation and say, 'Thanks, doc. I needed that,'" he said. "What we think it's going to do is restore the function of dopamine neurons that have been injured by the disease, but not killed. So if the cell has been destroyed and reabsorbed into the body, it's gone and there's nothing we can do."

Functional restoration could mean less severe symptoms when patients are off their standard Parkinson's disease medications.

"We're looking to see what Parkinson's disease looks like when they've been without their medications overnight," Nutt said. "We'll be clinically evaluating the signs of Parkinson's disease symptom changes, if there are any at all, and how the quality of life has improved."

The trial also is a test of whether therapeutic genes can be delivered into the nervous system, made to function and beneficial against neurological disease.

"If this fails, there are two questions: Did the gene really take, or have we not selected the right gene?" Nutt said. "Maybe we didn't select the optimal gene to affect Parkinson's disease."

Participation in the study is expected to take about 13 months, involving a one-month eligibility evaluation period and 12 months of follow-up visits.

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