Researcher Earns $300K Hartwell Award to Develop Potential Fragile X Syndrome Therapy

A University of Virginia scientist has won the Hartwell Individual Biomedical Research Award for her work on neurodevelopmental disorders that occur during childhood. The research of Sanchita Bhatnagar, PhD, will be funded with $100,000 per year for three years.

Bhatnagar is one of 12 recipients from 10 institutions to receive the award given by The Hartwell Foundation.

Bhatnagar’s lab is investigating a new therapy for young girls who have neurodevelopmental disorders due to gene defects on the X chromosome, including fragile X syndrome and Rett syndrome.

“I propose a novel therapeutic strategy to compensate for X‑linked gene deficiencies in young girls affected with NDD (neurodevelopmental disabilities) that will boost the expression of healthy genes from their dormant X chromosome and reverse the behavioral deficits,” Bhatnagar said in a press release.

Chromosomes come in pairs; one copy is inherited from the mother, the other from the father. Males are determined by a pair of X and Y chromosomes, while females are determined by a pair of two X chromosomes.

During female embryonic development, one of the two X chromosomes is randomly silenced in all cells except the egg cells. This process, called X-chromosome inactivation, occurs to balance the number of active genes present in the X chromosome for females and males.

Females with defective X chromosome genes, including mutations in the FMR1 gene (which causes fragile X) also carry a functional copy of the gene in their inactive X chromosome which, if reactivated, could substitute for the defective gene and treat the disease.

Bhatnagar is testing the effectiveness of lead compounds to reactivate functional genes present in the silent copy of X chromosome. These compounds are being evaluated in a nerve cell line obtained from a female patient with fragile X syndrome and in a mouse model of Rett syndrome.

She already identified a number of compounds that are effective in X-chromosome reactivation and can now be tested as therapeutics to treat neurodevelopmental diseases.

The approach is based on previous discoveries by the researcher that focused on studying the mechanisms underlying X chromosome inactivation in girls. She found that some factors involved in this process can be manipulated to reactivate X-linked genes without damaging cells, even in late stages of growth and development.

“If I am successful in identifying safe and effective drug candidates, it will lay a foundation for subsequent clinical trials and the latent potential to establish a cure,” Bhatnagar said.

“Effective and efficient compensation of X-linked gene deficiencies in young girls with NDD would bring emotional relief to affected families that would be immeasurable,” she said.

“The Hartwell Foundation seeks to inspire innovation and achievement by offering individual researchers an opportunity to realize their professional goals. Our approach is to be unique, selective, thorough and accountable. We provide an opportunity for those we support to make a difference and to realize their hopes and dreams,” said Fred Dombrose, president of the Hartwell Foundation.