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Gene therapy 'turns off' mutation linked to Parkinson's disease

A group of Northwestern University researchers is developing a novel gene therapy aimed at selectively turning off one of the genes involved in the development of Parkinson's disease.

The gene therapy, described in the January online issue of the journal Experimental Neurology, was designed by Martha Bohn and her laboratory group at Northwestern University Feinberg School of Medicine.

Bohn is Medical Research Council Professor and director of the neurobiology program at Children's Memorial Research Center and professor of pediatrics and of molecular pharmacology and biological chemistry at the Feinberg School. The gene technique the Bohn lab developed removes a protein known as alpha-synuclein from the diseased dopamine-producing neurons that die in Parkinson's disease. Alpha-synuclein is abundant in structures known as Lewy bodies ?a diagnostic hallmark of Parkinson's disease.

Research has shown that mutant forms of the alpha-synuclein gene, as well as too much alpha- synuclein protein, are involved in the development Parkinson's disease in some families.

For this research, the Bohn lab combined a recently developed technology called "RNA interference" with gene therapy to turn off alpha-synuclein in dopamine neurons. RNA interference is a sophisticated method to selectively turn off one gene in a cell, leaving others unaffected.

By placing the RNA interference into a crippled, non-disease-causing virus, scientists in the Bohn lab have been able to deliver the RNA interference tool to the brain of rats and turn off the alpha-synuclein protein in neurons. "This is the first step in developing a new therapy for Parkinson's disease based on molecular knowledge of the disease," said Mohan K. Sapru, research assistant professor of pediatrics, who is first author on the study and co-inventor of the gene therapy technology.

"It may also be useful for other diseases of the brain, such as dementia with Lewy bodies, a disease also characterized by Lewy bodies in the brain," Sapru said.

The Bohn lab will subsequently test this gene therapy in mouse models of the disease. If the RNA interference approach works in the mouse, a gene therapy based on silencing the _alpha-synuclein gene will be developed for clinical trials for Parkinson's patients.


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Source:Northwestern University


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