Pharmacotherapy for Fragile X Syndrome: Progress to Date

Matthew H. Davenport, Tori L. Schaefer, Katherine J. Friedmann, Sarah E. Fitzpatrick, Craig A. Erickson

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-15
Number of pages15
JournalDrugs
DOIs
StateAccepted/In press - Feb 8 2016
Externally publishedYes

Fingerprint

Fragile X Syndrome
Fragile X Mental Retardation Protein
Drug Therapy
Metabotropic Glutamate 5 Receptor
Pharmaceutical Preparations
Therapeutics
Synaptic Transmission
gamma-Aminobutyric Acid
Molecular Biology
Glutamic Acid
Placebos
Outcome Assessment (Health Care)
Brain
Population

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Davenport, M. H., Schaefer, T. L., Friedmann, K. J., Fitzpatrick, S. E., & Erickson, C. A. (Accepted/In press). Pharmacotherapy for Fragile X Syndrome: Progress to Date. Drugs, 1-15. https://doi.org/10.1007/s40265-016-0542-y

Pharmacotherapy for Fragile X Syndrome : Progress to Date. / Davenport, Matthew H.; Schaefer, Tori L.; Friedmann, Katherine J.; Fitzpatrick, Sarah E.; Erickson, Craig A.

In: Drugs, 08.02.2016, p. 1-15.

Research output: Contribution to journalArticle

Davenport, MH, Schaefer, TL, Friedmann, KJ, Fitzpatrick, SE & Erickson, CA 2016, 'Pharmacotherapy for Fragile X Syndrome: Progress to Date', Drugs, pp. 1-15. https://doi.org/10.1007/s40265-016-0542-y
Davenport MH, Schaefer TL, Friedmann KJ, Fitzpatrick SE, Erickson CA. Pharmacotherapy for Fragile X Syndrome: Progress to Date. Drugs. 2016 Feb 8;1-15. https://doi.org/10.1007/s40265-016-0542-y
Davenport, Matthew H. ; Schaefer, Tori L. ; Friedmann, Katherine J. ; Fitzpatrick, Sarah E. ; Erickson, Craig A. / Pharmacotherapy for Fragile X Syndrome : Progress to Date. In: Drugs. 2016 ; pp. 1-15.
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