Mutant gene predicts common Parkinson's

Friday, February 25, 2005

Jacksonville, Florida — A genetic mutation has been linked with typical, late-onset Parkinson's in a step towards new drugs that target particular forms of the disease.

American and European researchers led by neuroscientists at the Mayo Clinic in Jacksonville, Florida discovered the mutation in a recently identified gene called LRRK2 that previous studies have already linked to some forms of Parkinson's.

The mutation, dubbed G2019S, is the first, the researchers say, to be associated with typical, late-onset Parkinson's.

"From a research point of view, this is the first time we could identify what appears to be typical Parkinson's disease cases before people develop symptoms," says Mayo Clinic neuroscientist Matthew Farrer. "We know if someone inherits the mutation they are going to get Parkinson's disease."

The mutation was discovered by sequencing the LRRK2 gene in families with Parkinson's from the US, Norway, Ireland and Poland.

It was found in 22 of 42 family members of people with Parkinson's while it was absent in more than 2,000 healthy controls.

All people with G2019S mutations shared a genetic pattern indicating a common, ancient ancestor.

The finding shows that the most common form of Parkinson's disease, which was thought to be sporadic, has a genetic component.

While it's a small number of cases, says Farrer, the finding should help in the creation of Parkinson's models.

Farrer and colleagues are also starting to examine the cellular role of the LRRK2 protein and why the mutant gene causes disease.

"It's an exciting time in the study of the genetics of Parkinson's disease," says Farrer, who notes that there are already clinical trials of drugs called mixed-lineage kinase inhibitors that may be targeted at the form of the disease linked with the mutation.

The research is reported in the American Journal of Human Genetics.

Sources

Kachergus et. al. "Identification of a Novel LRRK2 Mutation Linked to Autosomal Dominant Parkinsonism: Evidence of a Common Founder across European Populations" — American Journal of Human Genetics, February 24, 2005
"Researchers find a mutation in LRRK2 gene causes Parkinson's disease in several North American and European families" — Mayo Clinic press release, February 25, 2005

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