Targeting Serotonin 1a Receptors During Development to Reverse Neurobehavioral Phenotypes in Fmr1 KO Mice
Khaleel Razak, PhD
Principal Investigator
Katilynne Croom
FRAXA Fellow
University of California at Riverside
Riverside, CA
2022-2024 Grant Funding: $100,000
Summary
Many people are familiar with drugs that target the brain’s serotonin receptors, such as Prozac, Zoloft, and Luvox. Drugs which increase serotonin levels are widely prescribed to treat anxiety and depression.
With this grant from FRAXA, Dr. Razak and his team will test an investigational new drug from Neurolixis in mice bred to model Fragile X syndrome. This new drug targets just one subtype of serotonin receptor: serotonin 1A.
Studies from multiple labs suggest that targeting this one type is a powerful approach to treating Fragile X syndrome. The goal of this grant is to gather enough preclinical evidence to move this drug forward to Fragile X clinical trials.
The Science
The proposed studies will test the efficacy of a novel and selective serotonin 1A (5HT1A) receptor agonist, NLX-101, in reversing a broad array of neurobehavioral outcomes in Fmr1 KO mice, a preclinical model of Fragile X syndrome (FXS). We will address three major issues that will facilitate the transition of the drug through the pre-clinical to clinical pipeline.
- We will determine if repeated administration of the drug is effective.
- We will test the hypothesis that repeated administration during early development will have long-lasting benefits into adulthood.
- We will evaluate the target specificity in reversing symptoms by comparing the effects of NLX-101 with those of less selective modulators of 5HT1A receptors.
By testing functional EEG measures that are remarkably similar across rodent models and humans with FXS, and behavioral measures that engage hyperactivity, social and cognitive control circuits, our data will provide guidance on which outcomes are sensitive to the different treatments provided at different ages. The long-term goal of these studies is to obtain sufficient preclinical evidence to move NLX-101 to clinical trials with data-driven guidance on administration time points and outcome measures to test.
