arbaclofen-placarbil and Fragile-X-Syndrome

Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism.

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Baclofen; Brain-Derived Neurotrophic Factor; Central Nervous System Stimulants; Clinical Trials as Topic; Dendritic Spines; Donepezil; Dopamine; Enzyme Inhibitors; Fragile X Mental Retardation Protein; Fragile X Syndrome; Humans; Indans; Lithium Compounds; Melatonin; Mice; Mice, Knockout; Minocycline; Nootropic Agents; Piperidines; Receptor, Metabotropic Glutamate 5; Receptors, GABA; Receptors, Metabotropic Glutamate; Signal Transduction; Vitamin E

Intellectual disability (ID; mental retardation) is considered an immutable condition. Current medical practices are aimed at relieving symptoms and not at altering the underlying cognitive deficits. Scientific advancements from the past decade have led to the exciting possibility that ID may now be treatable. Moreover, pharmaceutical therapies targeting the most common form of inherited ID, Fragile X syndrome (FXS), may become the new benchmark for central nervous system (CNS) drug discovery: seeking cures for neurodevelopmental disorders.

Topics: Allosteric Regulation; Animals; Baclofen; Central Nervous System Agents; Drug Discovery; Fragile X Syndrome; Humans; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate; Treatment Outcome