Biomarker Discovery and Validation for Fragile X Syndrome

With a $60,000 grant from FRAXA Research Foundation awarded 2015 and renewed in 2016, Dr. Eric Klann of New York University investigated potential new biomarkers in fragile X syndrome and how to translate these markers from mouse models to human patients.

$60,000 Grant
Eric Klann, PhD
Principal Investigator
Aditi Bhattacharya
Co-Principal Investigator

Aditi Bhattacharya, PhD
Co-Principal Investigator
National Centre for Biological Sciences
Bangalore, India

New York University
2016 FRAXA Research Grant
$120,000 over 2 Years

Drug development efforts for fragile X syndrome (FXS) have recently suffered significant setbacks with the under-performance of recent clinical trials. The FXS clinical and research community has scrutinized the outcome of these trials to better understand the reasons for their disappointing results and to propose better strategies for future therapeutic development efforts. From these discussions, there is a consensus that there is a lack of unbiased outcome measures to adequately evaluate the performance of new therapeutics in clinical trials. Hence, there is a critical need to develop reliable and relevant biomarkers to examine the efficacy of new therapeutics currently in development.

Because protein synthesis changes have been previously implicated in fragile X syndrome pathology in animal models and humans, we asked if differences in protein expression could provide key candidates for biomarkers in human patients. To examine changes in proteins in the brains of FXS model mice, we developed a combinatorial proteomic technique to detect and quantify changes in the landscape of basal and activity-protein synthesis. We applied this technique to analyze the protein expression profile of FXS model mouse hippocampi versus wild-type littermates, which has yielded candidates that can be potentially employed as biomarkers.

With funding from this program grant from the FRAXA Research Foundation, we aim to develop a biomarker system that is a) easy to perform across multiple sites, b) can be applied to a heterogeneous patient population, and c) would be capable of providing unbiased metrics for monitoring patient performance and response to therapies, independent of behavioral and psychological tests. In addition, we will determine which potential biomarkers identified in FXS animal models translate to the clinic, both from new candidates from our proprietary screen and those previously identified in FXS literature. Results from these studies will provide valuable information to characterize the limits of extrapolation at the molecular level from pre-clinical models to human disease states. We also hope to create a biomarker system that can be used for evaluation of efficacy and patient stratification to streamline interpretation of future clinical trial data.

Heather Bowling, PhD
Postdoctoral Fellow

New York University
2012 FRAXA Research Grant
$90,000 over 2 Years

This team examined the mTor pathway in Fragile X – which is also known to be defective in several forms of autism. Their work was published in September 2012 and received international attention.

A new method – genetically reducing S6K1 – has reduced several social, behavioral, and physical problems associated with fragile X syndrome in mice. “We think these results set the stage for a viable pharmacological approach to target S6K1, with the aim of diminishing or even reversing the afflictions associated with fragile X syndrome,” says Eric Klann. See NYU press release

Previous FRAXA Awards to the Klann Lab:

$45,000 in 2010

$55,000 in 2008, renewed for $55,000 in 2009

$60,000 in 2005, renewed for $60,000 in 2006

$57,000 in 2004

$40,000 in 2003

Previous Postdoctoral Fellows:

Hanoch Kaphzan, MD, PhD (2008-2010)

Lingfei Hou, PhD (2004-2005)

Explore Current Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.