Locking up iron in brain cells could prevent Parkinson's disease, according to a new study. It finds that preventing cellular damage caused by iron, using either a naturally occurring protein or an iron-binding drug, can slow the progression of the devastating disease. The catch is that the drug, when bound to iron, poisons nerve cells.
Parkinson's disease destroys nerve cells in a region of the brain called the substantia nigra, resulting in the jerky movements and tremors that characterize the disease. These neurons apparently deteriorate because of damage produced by oxidation of the brain chemical dopamine. Iron, if it's not properly restrained in the cell, can speed up the creation of destructive oxygen molecules. Patients with Parkinson's disease have more iron in their brains than people without the disease, but researchers have not been sure whether the disease causes the iron buildup or vice versa.
Neurobiologist Julie Andersen of the Buck Institute for Age Research in Novato, California, and her colleagues investigated two ways to tie up loose iron in the brains of mice with a Parkinson-like disorder. First, they injected mouse embryos with a human gene that encodes an iron-binding protein called ferritin. They engineered the gene so that only cells in the substantia nigra and related brain regions would produce the protein. Fewer neurons broke down in the mice than in untreated animals. Then the team tested the effect of the drug clioquinol, which binds iron and zinc. Researchers have previously shown it to slow down the progress of Alzheimer's disease. Mice given clioquinol orally lost fewer brain cells than mice who didn't receive the drug. Both clioquinol and ferritin treatments also preserved the mice's motor skills, the researchers report in the 27 March issue of Neuron.
Some controversy surrounds clioquinol, however; the drug was banned after its use as an antibiotic appeared to cause a neurodegenerative disorder in some Japanese patients. Andersen and colleagues suggest that vitamin B-12 deficiency caused the toxic effects, and that giving patients supplemental B-12 would eliminate the problem. Still, dermatologist Jack Arbiser of Emory University in Atlanta, Georgia, urges caution. "They've never proven that B-12 is the issue," he says. Regardless of whether clioquinol itself proves to be useful, "this should certainly spur efforts to find methods of intervening at the level of the iron," says Alzheimer's disease researcher Gregory Cole of the University of California, Los Angeles.