Evaluating the Effects of Selected Small-Molecules on a Zebrafish Model of TBCK Syndrome
Awardee: Gerald B. Downes
Institution: University of Massachusetts Amherst
Grant Amount: $50,400
Funding Period: February 1, 2022 - January 31, 2023
Summary:
TBCK Syndrome is a rare, poorly understood, severe neurological disease. In 2016 multiple publications first reported that mutations in the TBCK gene result in a progressive loss of muscle tone, intellectual disability, characteristic facial features, drug resistant epilepsy, and a high incidence of childhood or adolescent mortality. Outside of managing symptoms, there are currently no treatments to slow the progression of the disease. Animal models are often a key step towards better understanding a disease and developing new therapeutics, however there are currently no published animal models of TBCK Syndrome. Zebrafish are a widely used disease model due to several advantageous features, which also make this an excellent system to evaluate or screen for new therapeutic drugs. My laboratory is establishing a zebrafish model of TBCK Syndrome, and we have already created multiple tbck mutant lines and identified a phenotype. Our goals here are to continue characterizing the effects of tbck mutation on the zebrafish nervous system and to evaluate whether any of three different small-molecules, already FDA approved or known to be safe for human consumption, decrease the severity of tbck-mutant phenotypes. The completion of this project will establish a foundation to use zebrafish for small-molecule screens and help determine whether any of these compounds should be further investigated as a treatment for TBCK Syndrome.