Meltdown no more? Targeting Hypersensitivity in Fragile X

University of California Researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, Explore Drug Combinations to Limit Hypersensitivity to Sounds in Fragile X Mice

We’ve all been there.

Our child with Fragile X hears something and becomes excited.

Very excited.

Hand flapping follows with non-stop jumping and ear-piercing squawking.

Nothing helps.

No meds. No iPhone. No magic toy.

Several minutes go by. Sometimes longer.

How many times have you apologized in a grocery store — or restaurant — or at the mall? Wouldn’t it make our lives better if this unpredictable excitability was minimalized or eliminated?

That’s the premise behind research being conducted at University of California, Riverside. Principal Investigator Khaleel Razak, PhD, and postdoctoral fellow Jonathan W. Lovelace, PhD, are studying mice genetically altered to mimic the genetic characteristics of humans with Fragile X Syndrome. Their focus is on the mouse brain’s electrical activity when different kinds of sounds are present to provide insights on how humans with FXS may process sensory input. Their results may shed some light on aspects of attention, arousal and language.

“With similarities in auditory hypersensitive responses in humans and mice, this gives us a strong measure of comparison to test a series of drugs in novel combinations to treat FXS symptoms,” said Razak, associate professor, UC Department of Psychology. “Our results in mice are directly applicable to tests that can be conducted in a clinical setting and allow faster testing of drug effectiveness in the future.”

Research goals are to identify electrical measures in the brains of Fragile X model mice that are comparable to those in humans with FXS and test the effectiveness of different drug combinations that can bring brain activity back to a more normal range.

“These new measures will facilitate preclinical drug tests and development, and identify how drug combinations can be effective in treating symptoms,” said Lovelace, who works in UCR’s Neuroscience Program and collaborates with many labs across the country to find FXS drug treatments. Our research will allow for a much faster and translatable process for testing effective drugs in mice before they are moved to human trials.”

Multiple drug combinations will be tested for effectiveness in normalizing these measures, with the key being finding unique targets and tests for drugs that can be used to treat neurodevelopmental disorders.

“We want to ensure reproducible measures in mice that can be directly applied to humans,” Razak said. “Many different aspects of the experiments we conduct need to be precisely and carefully controlled. Identification of outcome measures that are analogous in mice and humans has been an obstacle in drug discovery in the past, including treatments for FXS.”

If successful, the research will establish reliable electrical brain measures in awake mice that can also be seen in humans. The results should help researchers in other labs conducting FXS research across the globe to apply it to their drug treatment research.

“The idea of collaboration for a direct immediate impact is much more real and motivating for my research on Fragile X,” Lovelace said. “The strong possibility of examining drug effects at circuit level is very exciting.”

Both researchers credit FRAXA with making this research possible.

“FRAXA funding will allow us to expand our current research in critical ways,” Lovelace said. “It will help us treat symptoms, expand work on testing these drugs on multiple mouse behaviors to provide relevant outcome measures and find an immediate drug treatment.”

In other words, keep calm.

To quote The Little River Band, “help is on its way.”

Dr. Jonny Lovelace and Dr. Khaleel Razak

Funding opportunities - FRAXA investigators
THE AUTHOR
Ted Coutilish and his son, Andrew

Theodore G. Coutilish is Vice Chancellor for Marketing and Community Relations at Oakland Community College in Michigan. Coutilish has enjoyed more than two decades of higher education marketing communications leadership experience.

Over the years, his peers have recognized his work with numerous prestigious awards, including IABC Detroit’s 2012 Communicator of the Year, the chapter’s highest honor, recognizing lifelong professional communications excellence. He lives in the City of Grosse Pointe, Michigan, with his wife, Mary Beth, and their son, Andrew, who has autism and Fragile X syndrome. He earned a MA from University of Detroit Mercy in 1994 and a BA in print journalism in 1987 from Wayne State University.

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