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Sourial M, Cheng C, Doering LC. Progress toward therapeutic potential for AFQ056 in Fragile X syndrome. J Exp Pharmacol. 2013;5:45-54doi: 10.2147/JEP.S27044.
Sourial, M., Cheng, C., & Doering, L. C. (2013). Progress toward therapeutic potential for AFQ056 in Fragile X syndrome. Journal of experimental pharmacology, 545-54. https://doi.org/10.2147/JEP.S27044
Sourial, Mary, et al. "Progress toward therapeutic potential for AFQ056 in Fragile X syndrome." Journal of experimental pharmacology vol. 5 (2013): 45-54. doi: https://doi.org/10.2147/JEP.S27044
Sourial M, Cheng C, Doering LC. Progress toward therapeutic potential for AFQ056 in Fragile X syndrome. J Exp Pharmacol. 2013 Jul 16;5:45-54. doi: 10.2147/JEP.S27044. eCollection 2013. PMID: 27186135; PMCID: PMC4863540.
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J Exp Pharmacol. 2013 Jul 16;5:45-54. doi: 10.2147/JEP.S27044. eCollection 2013.

Progress toward therapeutic potential for AFQ056 in Fragile X syndrome.

Journal of experimental pharmacology

Mary Sourial, Connie Cheng, Laurie C Doering

Affiliations

  1. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

PMID: 27186135 PMCID: PMC4863540 DOI: 10.2147/JEP.S27044

Abstract

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading single-gene cause of autism. It is caused by the lack of production of the Fragile X mental retardation protein (FMRP), resulting in cognitive deficits, hyperactivity, and autistic behaviors. Breakthrough advances in potential therapy for FXS followed the discovery that aberrant group 1 metabotropic glutamate receptor (mGluR) signaling is an important constituent of the pathophysiology of the syndrome. Research has indicated that upon neuronal stimulation, FMRP acts downstream of group 1 mGluRs (mGluRs1/5) to inhibit protein synthesis, long-term depression, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor internalization. To offset the deficits caused by the lack of FMRP, many pharmaceutical companies have designed medicinal drugs to target the unrestrained stimulation of mGluR5 signaling in FXS. Indeed, promising results from animal and clinical studies suggest that mGluR5 antagonists such as AFQ056 can successfully correct many of the deficits in FXS. In this review, we cover the animal studies performed to date that test the role of AFQ056 as a selective mGluR5 antagonist to alleviate the phenotypes of FXS.

Keywords: AFQ056; FMR1; Fmr1 knockout mouse; Fragile X mental retardation protein; Fragile X syndrome; group 1 metabotropic glutamate receptor 5 antagonist

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