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Therapeutic Strategies

In FXS, the absence of normal translational repression by FMRP results in excessive protein synthesis, affecting many brain functions. Dr. Richter’s lab at the Li Weibo Institute for Rare Diseases Research investigates how this excessive protein synthesis occurs. They have found that rebalancing protein synthesis can restore the behavioral and biochemical abnormalities of the syndrome in mouse models of FXS. By uncovering the underlying molecular basis of FXS, with a focus on mRNA translational control, the Richter lab ultimately aims to determine whether their findings in mouse models can be applied to developing treatments for FXS in human patients.


In a different approach, Drs. Green and Fang are working to identify factors that are involved in silencing, or inactivating, the FMR1 gene. Based on this information, they find small molecule inhibitors of these factors, which can restore gene expression. The Green Lab has shown that small molecule inhibitors can reactivate expression of FMR1 in neurons derived from induced pluripotent stem cells, and can correct characteristic molecular (e.g., neuronal gene expression, neuronal morphology) and electrophysiological (e.g., neuronal hyperexcitability) abnormalities of the syndrome. Essentially, this research adopts a therapeutic approach that is designed to correct the root cause of FXS.

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Optimization of ribosome profiling using low-input brain tissue from fragile X syndrome model mice

Authors: Liu B, Molinaro G, Shu H, Stackpole EE, Huber KM, and Richter JD


Published in 2019 in Nucleic Acids Research


This study used translational dysregulation in a mouse model of FXS to optimize ribosome profiling, a valuable tool for studying mRNA translation, so that the tool can capture subtle but biologically significant differences in translation in neurodevelopmental disorders. These findings pave the way for the application of ribosome profiling in future investigations of FXS.

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Fragile X Investigators

Michael Green

Michael Green, MD, PhD

Chair and professor of molecular, cell & cancer biology, Lambi and Sarah Adams Chair of Genetic Research, Co-director of the Li Weibo Rare Diseases Research Institute, Vice Provost for Strategic Research Initiatives

Green Lab

Joel Richter, PhD

Joel Richter, PhD

Professor of molecular medicine, Arthur F. Koskinas Chair in Neuroscience

Richter Lab

Minggang Fang, PhD

Minggang Fang, PhD

Assistant professor of molecular, cell and cancer biology

Website

Clinical Trials

At the Li Weibo Institute for Rare Diseases Research, our researchers and clinicians are dedicated to finding new treatment options for patients. Our clinical trials program is another way we continue to advance treatments and make new discoveries. If you or someone you know may be interested in a clinical trial, please subscribe for updates and you will be notified when we open up a new trial.

 

Research That Gives Hope

Optimizing Genome Editing Technologies for Therapeutic Application

By Scot A. Wolfe, PhD

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The research in my laboratory is focused on improving genome editing technologies so that they can be applied to the development of therapeutics. Inspired by the opportunity to improve the lives of patients with debilitating disorders, my lifelong goal as a scientist is to translate genome editing technologies to the development of therapeutics for a variety of diseases, both common and rare.

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A Potential Therapeutic Approach to CDKL5 Deficiency and Rett Syndrome

By Michael R. Green, MD, PhD

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Several years ago, we began investigating the mechanism by which genes are turned off on the X chromosome — a process termed X chromosome inactivation (XCI). In females, XCI is a naturally occurring phenomenon in which one of the X chromosomes is randomly turned off, or silenced, as a way to equalize the dosage of the X chromosome between females (who have two X chromosomes) and males (who have one).

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