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Dissected Brains of Fruit Flies Provide Clues in Autism Research

Published: Thursday, January 29, 2009
Last Updated: Monday, February 02, 2009
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A new bioassay methodology identifies drugs that may increase the cognitive functionality of children with mental retardation or autism.

Dr. Linda Restifo in Arizona Research Laboratory's (ARL) Division of Neurobiology has developed a promising methodology that uses fruit fly brains to screen for drugs that may increase the cognitive functionality of children with mental retardation or autism. The fruit fly brain has similar proteins and developmental mechanisms to those in human brains.

Restifo is testing drugs that are already approved by the FDA to determine whether and how well those drugs can change the size or shape of genetically abnormal brain neurons.

In a recently completed experiment, Restifo and her research team found several dozen drugs that straighten out curly brain neurons. The curliness results from lack of a protein that is thought to be important to brain development. The resounding success of the proof-of-concept study suggests a novel strategy for finding safe and effective drug treatments for mental retardation and autism in people.

Restifo is the first to use primary neuron culture for drug screening of this type. To conduct her research, Restifo and members of her lab monitor the size and shape of individual brain cells that have been dissected from the brain of a developing fruit fly at the maggot stage and allowed to grow in a laboratory culture dish. Each group of cells is treated with a single drug. The drugs selected for use by Restifo come from a collection of ~ 1,000 known drugs, most of which are already approved by FDA for other disease uses. In the neuron bioassay, cells are grown for three days and then observed under the microscope for changes the drug has caused in the size or shape of the neurons.

“Nobody is using a brain neuron assay in this way for drug screening.” commented Restifo. “The small size and short life cycle of fruit flies is advantageous at this stage. Over the next several years, we hope to move the experiments to mice and rats and eventually to human trials. It’s gratifying to think our research may identify drugs that help combat the behavioral and cognitive symptoms that affect children with mental retardation and autism. The therapeutic strategy does not promise a cure for autism, but rather the hope is to increase an individual’s functionality.”

“ARL is proud to support Dr. Restifo’s groundbreaking research,” said Michael Cusanovich, ARL Director. “Most assays don’t have a drug development slant and this has enormous potential as a demonstration project. Over the long-term, the fact the drugs in this study are being repurposed and are already FDA approved could make this effort an attractive investment opportunity. Dr. Restifo's medical background coupled with research focus in fruit fly genetics have enabled her to design a tremendously important methodology that may lead to therapeutic treatments for numerous neurological conditions, including autism.”

At the same time Restifo’s research has revealed FDA approved drugs that straighten out neuron curls, she has discovered that certain other drugs increase neuron curliness. Restifo is also currently conducting research to determine if drugs that increase neuron curliness would serve as treatments against certain invasive cancers, such as malignant glioma, the most deadly type of brain cancer. She is using the same neuron-culture methodology for the cancer and the autism projects, in both cases seeking therapeutic agents that change the shape of neurons from the fruit fly brain.

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