Baclofen is a GABA agonist that limits the release of presynaptic glutamate. It restores dendritic spine morphology, reverses AMPA receptor internalization, and corrects cognitive symptoms of Fragile X Syndrome.

Macalester College

Currently, there are no clinically proven treatments that directly affect the disease. Most proven treatments are for the comorbidities seen with Fragile X rather than the condition itself. However, there are many pharmacological treatments being tested for treatment of Fragile X - and many of these are already approved for treatment of other mental or physical conditions:
- Fenobam 
- Baclofen 
- Arbaclofen
- Acamprosate 
- Minocycline
- Lithium 
- MPEP
- CTEP
Some studies that use animal models have found ways to reduce the severity of symptoms like impaired cognition and seizures by conducting trials with metabotropic glutamate receptor 5 pathway antagonists. The severity of these symptoms correlate with the severity of the FMRP (fragile X mental retardation protein) deficit (Hagerman et al., 2009). Further research into this deficit and the methylation needed to prevent it may reveal more about possible treatments in the future.  

Emerging Treatments for Fragile X Syndrome

Sontheimer, H. (2015). Diseases of the Nervous System. Academic Press. 

Diseases of the Nervous System 

MPEP is a short-lived allosteric mGLUR5 blocker, which crosses the blood-brain barrier and acutely corrects the behavioral changes in *FMR1* knockout mice. It can even normalizes the abnormally increased protein expression in the hippocampus. This treatment, however, fails to chronically correct these symptoms because the half-life of the drug was too short. 


MPEP as a Possible Treatment for Fragile X Syndrome

CTEP is a mGLUR5 inhibitor and has a long half-life of 18 hours. It has been shown to reverse the Fragile X phenotype when given to mice at 5-6 weeks of age. 

CTEP as a Possible Treatment for Fragile X Syndrome

Fenobam is a mGLUR5 inhibitor and safely proven anxiolytic which has shown promise in a phase II open-label study.

Fenobam as a Treatment for Fragile X Syndrome

Baclofen as a Treatment for Fragile X Syndrome

Arbaclofen, related to baclofen, originally showed promise in a phase II, double-blind, placebo-controlled study but the subsequent phase III trial showed no improvement over the placebo.

Arbaclofen as a Treatment for Fragile X Syndrome

Acamprosate, a GABA agonist and approved treatment for alcohol withdrawal, showed promise in a small open-label trial on kids with Fragile X Syndrome and is now undergoing a larger placebo-controlled study.

Acamprosate as a Treatment for Fragile X Syndrome

Minocycline, an antibiotic, inhibits matrix metalloproteinase-9 normalizes dendritic spine morphology in mice. However, it only improved some of the symptoms in a small study done on kids aged 5 -17 with Fragile X Syndrome.

Minocycline as a Treatment for Fragile X Syndrome

Lithium, an approved treatment for bipolar disorder and depression, targets the upregulated GSK3 in Fragile X Syndrome and has been shown to significantly improve behavior in persons with Fragile X Syndrome.

Lithium as a Treatment for Fragile X Syndrome

Hagerman, R. J., Berry-Kravis, E., Kaufmann, W. E., Ono, M. Y., Tartaglia, N., Lachiewicz, A., Kronk, R., Delahunty, C., Hessl, D., Visootsak, J., Picker, J., Gane, L., &amp; Tranfaglia, M. (2009). Advances in the treatment of fragile X syndrome. Pediatrics, 123(1), 378–390. https://doi.org/10.1542/peds.2008-0317 

Learn Before

Related