A Link Between Leprosy and Parkinson's?

Bad bug. Mycobacterium leprae may wreak its havoc by interfering with cellular cleanup crews.

Leprosy is infamous for disfiguring its victims with boils and decaying flesh, but underlying the disease are degenerating nerves. Now researchers investigating a region of DNA that can render some people more susceptible to the scourge have found a potential link between leprosy and another neurodegenerative disease. The region includes part of two genes that have been linked to Parkinson's disease, suggesting the two disorders may share some biochemical pathways.

About 700,000 people in India, Brazil, and at least 16 other countries have leprosy. A microbe called Mycobacterium leprae causes the disease when it infects immune system cells known as Schwann cells and macrophages. Schwann cells insulate the nerves, and as the cells take ill, conduction through the nervous system falters. (Among other things, this degeneration blunts the pain caused by skin lesions making it more likely they will go untreated.) Some people seem to have a genetic susceptibility to the disease, and geneticists have homed in on a stretch of chromosome 6 that contains about 30 genes.

To identify the genes that confer susceptibility, human geneticist Erwin Schurr of McGill University in Montreal and colleagues took blood samples from 197 Vietnamese families. Then they examined genetic markers called single nucleotide polymorphisms (SNPs) within the chromosome 6 region. Schurr's team found that infected family members always inherited a particular stretch of DNA about 80 kilobases long, which differed from healthy relatives. The team then confirmed the results in 975 Brazilians.

The DNA stretch included two genes, PARK2 and PACRG, linked previously to Parkinson's disease. Mutations in PARK2 cause early-onset Parkinson's disease. The leprosy SNPs lie in the region of the DNA that turns the genes on and off. Both genes are involved in cleaning up cellular waste, a biochemical process not previously implicated in leprosy. Moreover, the proteins produced by PARK2 and PACRG loll around in Schwann cells and macrophages, supporting a role for them in leprosy, the team reported online 25 January in Nature.

"Nobody would have predicted this wonderful, serendipitous, exciting result," says human geneticist Michael Hayden of the University of British Columbia, Vancouver. He says the study "gets us thinking about the [human] genes involved in the pathogenesis of leprosy."

Related sites
Erwin Schurr's site
More on leprosy from the Centers for Disease Control and Prevention

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