Which is the right FMRP for Therapeutic Development of Fragile X Syndrome?
Samie Jaffrey, PhD
Principal Investigator
Wen-Biao Gan, PhD
Co-Investigator
Jiahui Wu, PhD
Postdoctoral Fellow
from Weill Medical College of Cornell University
New York, NY
2016-2017 Grant Funding: $90,000
Summary
Normally there are many forms of the Fragile X protein (FMRP) in brain cells. Dr. Jaffrey is working to identify the forms that are most important as treatment targets.
The Results
Research from this project clarified that the Fragile X protein (FMRP) plays distinct roles in different parts of the neuron, helping explain why its loss has widespread effects in Fragile X syndrome. The team showed that FMRP is present in the nucleus, where it appears to protect the genome; in the cell body, where it influences protein synthesis; and at synapses, where it helps regulate communication between neurons.
Building on these insights, Dr. Jaffrey’s group developed experimental approaches to selectively restore FMRP in specific neuronal compartments in Fragile X mouse models. This work provides critical guidance for therapeutic development by identifying which locations and functions of FMRP are most important to restore, helping to focus future treatments on the molecular mechanisms most directly responsible for Fragile X syndrome.
The Science
A major challenge in developing therapeutics for Fragile X syndrome is the fact that normally there are many forms of the Fragile X protein (FMRP). This one protein regulates various pathways in different cell compartments of both neuronal and non-neuronal cells. It is difficult to determine which FMRP-regulated pathway needs to be corrected to improve clinical outcomes in FXS.
To definitively answer the above questions, we propose to develop a highly robust method to selectively restore protein expression in a compartment-specific and cell-specific
manner of live animals and determine if this reverses synaptic and spine defects. Our long-term goal is to indentify druggable targets for FXS therapeutic development.
Grant Post Revisions
- 2019/09 - Added The Results.
- 2016/05 - Original grant post published.