To Interrogate the Developmental Timing for Treating Fragile X Syndrome
Xinyu Zhao, PhD
Principal Investigator
Zhiyan Xu
FRAXA Fellow
Weiping Tang, PhD
Collaborator
University of Wisconsin
Madison, WI
2024-2025 Grant Funding: $100,000
Summary
Are there critical developmental ages in Fragile X syndrome? Is it ever too late to begin treatment? Will different treatment approaches be as successful in adults as in young children?
With this grant, the team will conduct studies to answer these important questions.
The Science
There have been many clinical trials for individuals with Fragile X syndrome and more planned in the near future for both gene therapy and drug treatments. However, the developmental timing for effective treatment of Fragile X has not been determined. A question that has been raised many times and remains unanswered is: are there developmental ages (critical periods) for the most effective treatment?
We will first use a transgenic mouse model that allows us to restore FMRP in all cells at precise developmental ages. The purpose of these studies is to determine the critical periods of FMRP restoration for correcting certain behavioral and cellular deficits. Next, because recent studies from our and others’ groups have discovered that Fragile X syndrome neurons have reduced mitochondrial functions and energy metabolism, we will evaluate the effects of two mitochondrial targeting treatments:
- Leflunomide, which can correct deficits in cultured human Fragile X neurons, and
- Nicotinamide mononucleotide, a dietary supplement showing efficacy for treating mouse models of Alzheimer disease.
By investigating the critical periods for genetic and drug treatment therapies, this project will answer a key question for therapeutic development for Fragile X syndrome. The outcome of this project should lead to more effective treatments for FXS, ultimately improving the quality of life for patients and their families.
