Neuromotor Outcome Measures for Clinical Trials in Fragile X Syndrome

With a $35,000 grant from FRAXA Research Foundation, Dr. Nicole Tartaglia from the University of Colorado Denver and Tracey Stackhouse aimed to develop neuromotor outcome measures for use in clinical trials in FXS, and to contribute to a deeper understanding of the neuromotor issues involved in FXS. This collaborative project was completed at the two sites of the Colorado Fragile X Clinic: The Children’s Hospital and Developmental FX. Dr. Nicole Tartaglia is the Medical Director of the Fragile X Clinic at The Children’s Hospital of Denver. Tracy Murnan Stackhouse, MA, OTR is the co-founder of the Developmental & Fragile X Resource Centre (Developmental FX), a clinic specializing in fragile X.

Stephen Haggarty, PhD, Harvard/MIT, Principal Investigator, FRAXA research grant

Small Molecule Modulators of Lithium for Treatment of Fragile X Syndrome

With a $219,500 grant from FRAXA Research Foundation, Dr. Stephen Haggarty from Havard/MIT developed a high-throughput drug screen to find compounds that inhibit GSK3, a critical enzyme in fragile X. He looked for compounds that can accomplish this either alone or in combination with lithium, offering the possibility of enhancing the effectiveness of lithium as a treatment. His drug screen used patient-specific neural progenitor (NP) cells derived from human induced pluripotent stem cells (iPSCs) – which are created from cells in a skin biopsy from people with fragile X syndrome (FXS) and other autism spectrum disorders.

Involvement of the miRNA Pathway in Fragile X Syndrome

With a $304,000 grant from FRAXA Research Foundation over several years, Drs. Oostra and deVrij from Erasmus University studied miRNA and fragile X. miRNAs are RNAs that can repress the translation of target mRNAs – therefore they can play a role in protein synthesis within the neuron. Preliminary results showed large differences in miRNA expression in the fragile X mouse brain compared to the wild type. This lab investigated the effect of mGluR5 antagonists on the levels of these specific miRNAs.

Basic Mechanisms of Disease and Potential Therapeutic Strategies

With $245,000 in grants from FRAXA Research Foundation, Dr. Stephen Warren and his lab at Emory University studied all aspects of fragile X syndrome, from the mechanisms of repeat expansion to high-throughput drug screens in the Drosophila model of fragile X. The Warren lab made the original discovery of the fragile X gene, FMR1, in collaboration with the Nelson and Oostra labs, and is recognized internationally as a leader in molecular genetics. Recent projects include establishment of induced pluripotent stem cell lines from fragile X patients, and determination of other forms of mutation in the fragile X gene, other than the most common trinucleotide repeat expansion.