title: Pharmacotherapy for Fragile X Syndrome: Progress to Date.
abstract: To date, no drug is approved for the treatment of Fragile X Syndrome (FXS) although many drugs are used to manage challenging behaviors from a symptomatic perspective in this population. While our understanding of FXS pathophysiology is expanding, efforts to devise targeted FXS-specific treatments have had limited success in placebo-controlled trials. Compounds aimed at rectifying excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission, as well as other signaling pathways known to be affected by Fragile X Mental Retardation Protein (FMRP) are under various phases of development in FXS. With the failure of several metabotropic glutamate receptor subtype 5 (mGlur5) selective antagonists under clinical investigation, no clear single treatment appears to be greatly effective. These recent challenges call into question various aspects of clinical study design in FXS. More objective outcome measures are under development and validation. Future trials will likely be aimed at correcting multiple pathways known to be disrupted by the loss of FMRP. This review offers a brief summary of the prevalence, phenotypic characteristics, genetic causes and molecular functions of FMRP in the brain (as these have been extensively reviewed elsewhere), discusses the most recent finding in FXS drug development, and summarizes FXS trials utilizing symptomatic treatment.
authors: Division of Child and Adolescent Psychiatry (MLC 4002), Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229-3039, USA.|Department of Biomedical Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, 45221, USA.
authors: Matthew H
authors: MH
authors: Davenport
authors: Division of Child and Adolescent Psychiatry (MLC 4002), Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229-3039, USA.
authors: Tori L
authors: TL
authors: Schaefer
authors: Division of Child and Adolescent Psychiatry (MLC 4002), Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229-3039, USA.
authors: Katherine J
authors: KJ
authors: Friedmann
authors: The Ohio State University, Columbus, OH, USA.
authors: Sarah E
authors: SE
authors: Fitzpatrick
authors: Division of Child and Adolescent Psychiatry (MLC 4002), Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229-3039, USA. craig.erickson@cchmc.org.
authors: Craig A
authors: CA
authors: Erickson
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid