Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Fragile X syndrome (FXS) is an inherited intellectual disability linked to autism.
• It results from the absence of the fragile X mental retardation protein (FMRP).
• Extensive research has identified molecular, cellular, and system-level defects in FXS.

Purpose of the Study:

• To summarize recent advances in understanding FMRP's molecular functions beyond mRNA binding.
• To describe current developments and limitations of the FXS mouse model for preclinical research.
• To review clinical trial outcomes and inform future FXS and autism spectrum disorder (ASD) therapy development.

Main Methods:

• Review of basic, preclinical, and translational clinical research.
• Analysis of molecular functions of FMRP.
• Evaluation of FXS mouse models and clinical trial data.

Main Results:

• Progress in understanding FMRP's diverse molecular roles.
• Insights into the utility and limitations of FXS mouse models.
• Review of recent clinical trial results, highlighting successes and challenges.

Conclusions:

• Recent research deepens understanding of FMRP and FXS pathophysiology.
• FXS mouse models offer valuable preclinical insights but have limitations.
• Clinical trial outcomes guide future therapeutic strategies for FXS and ASDs.