Scientists have discovered a new gene mutation that could account for Parkinson's disease in as many as 10,000 Americans.
The finding, confirmed in a series of studies published today in the online version of the British journal Lancet, could lead to the first genetic test for the disabling movement disorder, as well as a new generation of medicines.
"This is the most common genetic mutation identified in Parkinson's," said William Nichols of Cincinnati Children's Hospital Medical Center, co-author of one study. "Once we determine what the protein for the gene does, we can come up with novel treatments."
The only available treatments for Parkinson's reduce the symptoms, which include muscle stiffness, rigidity, slowed movements and impaired coordination. The gene identified in families affected by Parkinson's is called leucine-rich repeat kinase-2, or LRRK2. Kinases are enzymes that regulate genes by turning them on and off. The scientists are still trying to understand how the mutation leads to Parkinson's.
In November, Andrew Singleton, chief of molecular genetics at the National Institute on Aging, published the first observation of the LRRK2 mutation. In an international collaboration, Singleton and his colleagues discovered a change in a single amino acid in a gene sequence in five families with a history of Parkinson's -- one from London and four from the Basque region in Spain. In follow-up studies, scientists looked for the mutation in 130 other Parkinson's patients in the same area in Spain and found 7 percent had the exact mutation. Many had no family history of the illness.
This opened the door to the latest studies.
In one study, Tatiana Foroud and her colleagues at Indiana University School of Medicine tested 767 patients from 358 families, all of whom are part of a nationwide Parkinson Study Group. Five percent of them had this gene mutation.
"It may not sound like a lot, but it represents a lot of people," said Singleton, co-author of one of the Lancet papers. In another collaborative effort, he found the mutation in 1 percent to 2 percent of patients without a family history of the disease. This is the first time a gene has been associated with so-called sporadic cases of Parkinson's. In the past decade, five genes have been linked to inherited forms.
There are a million patients in the country with Parkinson's. Singleton said patients with this mutation develop symptoms around age 60 and live longer than other Parkinson's patients.
Scientists in several labs are trying to figure out what the gene does. "If we can follow the chain of events that lead to the disease, we can target treatments at this pathway," Singleton said.
The gene mutation may also provide insights into some forms of Alzheimer's dementia.
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