NIH Grant Supports Research Into Potential Targets for Fragile X Therapies

NIH Grant Supports Research Into Potential Targets for Fragile X Therapies
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Investigators at the Mercer University’s College of Pharmacy were awarded almost $425,000 in three-year funding to advance work into serotonin receptors as potential targets for preventing seizures in people with fragile X syndrome, according to a university news story.

The R15 grant is funded by the National Institute of Neurological Disorders and Stroke, a branch of the National Institutes of Health (NIH), and aims to support research in institutions providing baccalaureate or advanced degrees to scientists who have not yet received major NIH funding.

This grant’s principal investigator is Clinton Canal, PhD, a professor of pharmaceutical sciences and investigator at Mercer, who has conducted extensive research into how serotonin receptors are affected in people with this disease.

Fragile X results from mutations in the FMR1 gene, which provides instructions for making a protein known as FMRP. Its loss is associated with a range of symptoms in patients, including intellectual disability, attention deficits, anxiety, and hyperactive behavior. About one-third also experience seizures caused by loud noises or bright lights.

The serotonin system is one of the primary regulators of mood and anxiety, and appears to be altered in fragile X and autism spectrum disorder. Patients may be treated with medicines that manipulate the serotonin system, known as selective serotonin reuptake inhibitors that include the antidepressants fluoxetine (marketed as Prozac, among other brands) and sertraline, sold as Zoloft among other names.

However, there are at least 15 serotonin receptors, and many appear to control the brain circuits affected in neurodevelopmental and psychiatric disorders. Which of these could be therapeutic targets to provide meaningful benefits to fragile X patients remains unclear.

Canal received a $90,000 grant from the FRAXA Research Foundation in 2017 to investigate how the FMRP protein’s absence impacts the levels of serotonin receptors in neural systems affected by fragile X.

In previous published research working in a mouse model, Canal found that partially activating two serotonin receptors, 5-HT1A and 5-HT7, reduced stereotypy, or the involuntary, repetitive movements common in people with fragile X, in the animals.

The new project will focus on these two receptors.

“This new study will look at whether selectively activating serotonin 5-HT1A and selectively inactivating 5-HT7 receptors during an early developmental sensitive period prevents seizures and corrects alterations in brain activity in FXS [fragile X syndrome] mice,” Canal said.

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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