Scientists have created a mutant fruit fly that suffers from symptoms resembling adrenoleukodystrophy (ALD), a rare, fatal hereditary brain disease made famous by the 1993 movie Lorenzo's Oil. In that movie, which was based on a true story, one patient's parents set out to find a cure. Their brew of fatty acids didn't become the cure they had hoped for, but Lorenzo's oil can prevent neural decay in the mutant flies, researchers report  in this week's issue of Science. The finding might spark new research on the oil, and the flies could become valuable research tools.
The fly came out of a project led by Kyung-Tai Min and Seymour Benzer of the California Institute of Technology in Pasadena, who study fly mutations that mimic human neurodegenerative conditions. They mutated flies with P elements, little bits of DNA that jump around the fly's genome, inactivating genes. Next, they looked for mutants with shortened life-spans and examined them for signs of dying neurons. In one such mutant, one of the neural layers in the flies' eyes had an abnormal bubbly appearance.
The mutated gene turned out to encode a protein whose sequence suggests it is an acyl coenzyme A (CoA) synthetase, an enzyme that helps break down fatty acids. A similar enzyme is impaired in ALD, leading to high blood levels of very long chain fatty acids (VLCFAs) in patients and--for reasons poorly understood--progressive degeneration of brain cells. VLCFA levels proved to be high in the mutant flies, too.
The researchers tested whether the flies responded to Lorenzo's oil, a mixture of two fatty acids. In humans, the oil lowers VLCFA levels by slowing their synthesis, but it didn't slow down disease progression in clinical trials. Benzer and Min saw something similar when they treated flies with glyceryl trioleate oil, one of the components of Lorenzo's oil: VLCFA levels dropped, but neurons in the fly brains kept dying. When Min began treatment while the flies were still larvae, however, the symptoms stayed away. In humans, giving the oil before symptoms begin hasn't increased its effectiveness, perhaps because of the blood-brain barrier, which flies don't have.
The results may rekindle efforts to alter one of the compounds in Lorenzo's oil to enable it to enter the brain, says neurologist Hugo Moser, who studies ALD at the Kennedy Krieger Institute at The Johns Hopkins University School of Medicine in Baltimore. Even more importantly, the flies could be used to screen other drugs quickly. "Using the fruit fly as a model [for a human disease] is extremely exciting," he adds.