Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome

Erickson, Craig A.; Wink, Logan; Ray, Balmiki; Early, Maureen; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; Lahiri, Debomoy K.; McDougle, Christopher J.

doi:10.1007/s00213-013-3022-z

Cited by 88 publications

(51 citation statements)

References 62 publications

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“…An additional phase III trial in children with FXS showed promise but full analyses are pending. Acamprosate, currently Food and Drug Administration-approved for alcohol withdrawal, with agonist properties at both GABA-A and GABA-B receptors, has shown promise, in an open-label trial, for hyperactivity and social functioning in FXS [209]. Acamprosate and the GABA-A agonist ganaxolone are being tested in small placebo-controlled trials in FXS [203].…”

Section: Translation Of Targeted Treatments To Humans With Fxsmentioning

confidence: 99%

Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back

et al. 2015

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Fragile X syndrome (FXS), an inherited intellectual disability often associated with autism, is caused by the loss of expression of the fragile X mental retardation protein. Tremendous progress in basic, preclinical, and translational clinical research has elucidated a variety of molecular-, cellular-, and system-level defects in FXS. This has led to the development of several promising therapeutic strategies, some of which have been tested in larger-scale controlled clinical trials. Here, we will summarize recent advances in understanding molecular functions of fragile X mental retardation protein beyond the well-known role as an mRNAbinding protein, and will describe current developments and emerging limitations in the use of the FXS mouse model as a preclinical tool to identify therapeutic targets. We will review the results of recent clinical trials conducted in FXS that were based on some of the preclinical findings, and discuss how the observed outcomes and obstacles will inform future therapy development in FXS and other autism spectrum disorders.Key Words Fragile X syndrome . FMRP . mRNA translation . clinical trials . biomarkers . language development Fragile X syndrome (FXS) is one of the first single gene disorders manifesting features of autism spectrum disorder (ASD) in which extensive study of the neurobiology and synaptic mechanisms of disease in cellular and animal models has been possible. The enormous progress in basic and preclinical and clinical translational work in FXS in the last several decades has allowed FXS to emerge as an important model to illustrate successes and hurdles in the development of future targeted treatments for autism and related developmental disorders. FXS is the most common known genetic cause of intellectual disability and ASD, with an estimated frequency of about 1 in 4000-5000 [1]. The disorder affects all ethnic groups worldwide. Genetics and Phenotype of FXSFXS is one of the fragile X-associated disorders (FXDs), all of which arise from a trinucleotide repeat (CGG) expansion mutation in the promoter region of FMR1. The CGG sequence is transcribed into the 5' untranslated region of FMR1 mRNA and thus length of the repeat sequence does not affect the sequence of the protein product of FMR1 [fragile X mental retardation protein (FMRP)] [2]. Small expansions in the gene (55-200 CGG repeats), termed the Bpremutation^, occur in about 1 in 430-468 males and 1 in 151-209 females in the USA [3,4], and is associated with risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Although the premutation is transcribed and translated to give FMRP, toxicity in fragile X-associated tremor/ataxia

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Section: Translation Of Targeted Treatments To Humans With Fxsmentioning

confidence: 99%

Therapeutic Strategies in Fragile X Syndrome: From Bench to Bedside and Back

et al. 2015

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“…Although an alcohol treatment program can be effective (31) and there is an urge to find improved medications to treat alcohol dependence (32) this may not be available in a rural, poor setting such as seen in Ricaurte. Acamprosate, an FDA-approved drug for the maintenance of abstinence from alcohol use in adults is also a targeted treatment for FXS (33). Acamprosate has pleiotropic effects impacting glutamate and GABA neurotransmission (34).…”

Section: Casementioning

confidence: 99%

Alcohol use dependence in fragile X syndrome

Salcedo-Arellano

Lozano

Tassone

et al. 2016

IRDR

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“…These include agents targeting mGluR5, GABAA, the endocannabinoid system, and other signaling pathways such as insulin growth factor (IGF), MAPK/Erk, and BDNF (12,18,19,(60)(61)(62)(63). Symptom-based treatments currently include stimulants, antidepressants (e.g.…”

Section: Ssri Treatment In Fxsmentioning

confidence: 99%