Fragile X Syndrome (Martin Bell Syndrome)

A condition characterized genotypically by mutation of the distal end of the long arm of the X chromosome (at gene loci FRAXA or FRAXE) and phenotypically by cognitive impairment, hyperactivity, SEIZURES, language delay, and enlargement of the ears, head, and testes. MENTAL RETARDATION occurs in nearly all males and roughly 50% of females with the full mutation of FRAXA. (From Menkes, Textbook of Child Neurology, 5th ed, p226)

Also Known As:

Networked: 935 relevant articles (24 outcomes, 82 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Parkinson Disease (Parkinson's Disease)
2.	Autistic Disorder (Autism)
3.	Dyskinesias (Dyskinesia)
4.	Alzheimer Disease (Alzheimer's Disease)
5.	Mental Retardation (Idiocy)

Experts

1.	Bassell, Gary J: 22 articles (11/2015 - 03/2004)
2.	Warren, Stephen T: 21 articles (03/2015 - 05/2002)
3.	Tassone, Flora: 20 articles (07/2015 - 01/2004)
4.	Hagerman, Randi J: 16 articles (11/2014 - 01/2004)
5.	Jin, Peng: 16 articles (10/2014 - 03/2003)
6.	Willemsen, Rob: 16 articles (03/2014 - 05/2002)
7.	Oostra, Ben A: 16 articles (05/2012 - 05/2002)
8.	Bagni, Claudia: 15 articles (09/2015 - 02/2003)
9.	Neri, Giovanni: 14 articles (03/2014 - 04/2004)
10.	Greenough, William T: 14 articles (03/2011 - 05/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Fragile X Syndrome:

1.	LithiumIBA 06/18/2014 - "Lithium: a promising treatment for fragile X syndrome." 06/01/2011 - "Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome." 08/01/2008 - "Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome." 10/01/2013 - "Lithium treatment alleviates impaired cognition in a mouse model of fragile X syndrome." 10/01/2013 - "Our findings suggest that lithium might have a therapeutic effect in fragile X syndrome."
2.	Levodopa (L Dopa)FDA LinkGeneric 11/01/2014 - "The efficacy of AFQ056/mavoglurant in humans has been assessed in L-dopa induced dyskinesia in Parkinson's disease and Fragile X syndrome in proof of principle clinical studies." 11/01/2013 - "Given positive results in proof-of-concept studies in humans for certain indications such as levodopa-induced dyskinesia in Parkinson's disease, fragile X Syndrome, gastroesophageal reflux disease, migraine and anxiety, and the soaring chemical diversity among the mGlu5-negative allosteric modulators, there is reason to believe that a drug will emerge from this therapeutic class in the near future. " 04/01/2013 - "Potential roles have been established for mGlu5 NAMs in the treatment of diseases such as pain, anxiety, gastroesophageal reflux disease (GERD), Parkinson's disease levodopa-induced dyskinesia (PD-LID), fragile X syndrome (FXS), autism, addiction, and depression. " 01/01/2016 - "Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) have potential applications in the treatment of fragile X syndrome, levodopa-induced dyskinesia in Parkinson disease, Alzheimer disease, addiction, and anxiety; however, clinical and preclinical studies raise concerns that complete blockade of mGlu5 and inverse agonist activity of current mGlu5 NAMs contribute to adverse effects that limit the therapeutic use of these compounds. " 02/12/2015 - "Negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu5) have potential for the treatment of psychiatric diseases including depression, fragile X syndrome (FXS), anxiety, obsessive-compulsive disorders, and levodopa induced dyskinesia in Parkinson's disease. "
3.	MelatoninIBA 03/01/2009 - "Protective effects of melatonin against oxidative stress in Fmr1 knockout mice: a therapeutic research model for the fragile X syndrome." 04/15/2009 - "To determine the efficacy of melatonin on sleep problems in children with autistic spectrum disorder (ASD) and fragile X syndrome (FXS). " 12/11/2000 - "Melatonin profiles and sleep characteristics in boys with fragile X syndrome: a preliminary study." 03/01/1986 - "Melatonin profiles were studied in five males with cytogenetic and clinical features of the fragile-X syndrome including megalo-orchidia and macrogenitosomia. " 03/01/1986 - "Does melatonin deficiency cause the enlarged genitalia of the fragile-X syndrome?"
4.	Glycogen Synthase (Synthase I)IBA 01/01/2012 - "The role of glycogen synthase kinase-3 signaling in neurodevelopment and fragile X syndrome." 01/01/2014 - "Here we review evidence that inhibition of glycogen synthase kinase-3 (GSK3) ameliorates cognitive deficits in a wide variety of animal models of CNS diseases, including Alzheimer's disease, Fragile X syndrome, Down syndrome, Parkinson's disease, spinocerebellar ataxia type 1, traumatic brain injury, and others. " 02/15/2010 - "Lithium ameliorates altered glycogen synthase kinase-3 and behavior in a mouse model of fragile X syndrome."
5.	DNA (Deoxyribonucleic Acid)IBA 01/01/1994 - "Characterization of the mutations involved has greatly improved our knowledge of the transmission of fragile X syndrome and new DNA-based diagnostics tools significantly outperform cytogenetic testing both for establishing the diagnosis and for determining carrier status. " 06/01/2008 - "The purposes of this study were to present DNA analysis findings of our case series of fragile X syndrome (FXS) based on methylation-specific polymerase chain reaction (MS-PCR), PCR, and Southern blotting alongside developmental characteristics including psychological profiles and to review the literature on FXS in Korea. " 01/01/2007 - "In the present study, we analyzed the utility of PCR on modified DNA as a rapid screening method for diagnosis of patients with Fragile X syndrome and HD. " 01/01/2002 - "In this study, we screened DNA samples from 1205 patients originally referred for fragile X syndrome (FRAX) testing, because of MR of unknown etiology and detected 8 KS patients. " 07/30/1999 - "A maternal male second cousin had been identified with fragile X syndrome based on DNA studies. "
6.	Minocycline (Cyclops)FDA LinkGeneric 09/01/2010 - "As with any other treatments, we emphasize that randomized clinical trials are needed to determine the efficacy of minocycline in fragile X syndrome." 04/01/2013 - "A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome." 01/01/2010 - "Open-label add-on treatment trial of minocycline in fragile X syndrome." 10/01/2013 - "Minocycline normalizes synaptic connections and behavior in the knockout mouse model of fragile X syndrome (FXS). " 10/01/2013 - "Electrocortical changes associated with minocycline treatment in fragile X syndrome."
7.	BaclofenFDA LinkGeneric 08/01/2015 - "The selective GABAB receptor agonist R-baclofen previously reversed social deficits and reduced repetitive behaviors in a mouse model of Fragile X syndrome, and Arbaclofen improved some clinical symptoms in some Fragile X and ASD patients. " 07/01/2015 - "R-Baclofen Reverses a Social Behavior Deficit and Elevated Protein Synthesis in a Mouse Model of Fragile X Syndrome." 01/01/2012 - "STX209 is an exploratory drug comprising the single, active R-enantiomer of baclofen which is in later stage clinical trials for the treatment of fragile x syndrome (FXS) and autism spectrum disorders (ASD). " 06/01/2015 - "Drug discovery studies demonstrated that γ-aminobutyric acid (GABA)-related agonists (e.g., baclofen) will mitigate experimental myopia, and are also drugs studied for their capacity to affect neurodevelopmental disorders that include Fragile X Syndrome and related autism spectrum disorders. "
8.	alpha- Amino- 3- hydroxy- 5- methyl- 4- isoxazolepropionic Acid (AMPA)IBA 02/01/2015 - "7, 8-Dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome." 10/01/2006 - "Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial." 06/01/2015 - "Evidence that lens GABA receptors are expressed in a cell environment comparable to neurons is seen in the lens expression of AMPA and NMDA glutamate receptors together with an unexpectedly comprehensive array of associated signaling proteins that include post-synaptic-density 95 (PSD95), calcium calmodulin kinase IIα (CaMKIIα), Fragile X Syndrome mental retardation protein (FMRP), ephrin receptors, Ca(V)1.2, 1.3 channels, cyclin-dependent kinase 5 (Cdk5), and neuronal C-src among others. "
9.	Psychotropic Drugs (Psychoactive Drugs)IBA 01/01/2004 - "These limited studies and surveys of psychotropic drugs used in individuals with fragile X syndrome suggest that stimulants are helpful for hyperactivity, that alpha(2)-adrenoceptor agonists and beta-adrenoceptor antagonists help to control overarousability, impulsivity and aggressiveness, and that SSRIs can control anxiety, impulsivity and irritability, alleviate depressive symptoms and decrease aggressive and self-injurious behaviour. " 02/01/2014 - "These findings suggest that properly dosed and combined FDA-approved psychoactive drugs may effectively treat the cognitive impairment associated with fragile X syndrome. "
10.	Methotrexate (Mexate)FDA LinkGeneric 01/01/2013 - "Unless FMR1 reactivation is more effective in vivo our results indicate that methotrexate has no role in the treatment of fragile X syndrome." 01/01/2013 - "We show that it is possible to reactivate FMR1 transcription in fibroblasts of fragile X syndrome patients by treatment with methotrexate. " 01/01/2013 - "Fibroblasts of fragile X syndrome patients were treated with methotrexate in concentrations ranging from 1 to 4 μg/ml for up to 14 days. " 01/01/2013 - "The aim of the study was to analyze if methotrexate, an agent which also reduces DNA methylation but with less toxicity than 5-azadeoxycytidine, has therapeutic potential in fragile X syndrome. " 01/01/1984 - "Fragile X syndrome patient and carrier lines and normal control cell lines did not differ in regard to folate requirement for growth, the ability to use homocysteine in place of methionine, the ability to utilize reduced folates as the sole folate source, or methotrexate sensitivity. "

Therapies and Procedures

1.	Therapeutics 01/23/2013 - "Fragile X syndrome therapeutics: translation, meet translational medicine." 12/01/2012 - "Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics." 02/01/2015 - "Recognized as the most common inherited from of intellectual disability (ID) and the most common known monogenic cause of autism spectrum disorders (ASD), Fragile X syndrome (FXS) is identified as an unmet medical need for the development of personalized medicine and targeted therapeutics for neurodevelopment disorders as a result of improved understanding of the genetic and cellular mechanisms. " 04/12/2012 - "Fragile X syndrome therapeutics S(C)TEP through the developmental window."
2.	Individualized Medicine 02/01/2015 - "Recognized as the most common inherited from of intellectual disability (ID) and the most common known monogenic cause of autism spectrum disorders (ASD), Fragile X syndrome (FXS) is identified as an unmet medical need for the development of personalized medicine and targeted therapeutics for neurodevelopment disorders as a result of improved understanding of the genetic and cellular mechanisms. "
3.	Occupational Therapy (Therapy, Occupational) 01/01/2011 - "Most of the younger patients involved were also taking part in special education programmes (usually involving language and occupational therapy).We were not able to perform meta-analysis to combine results but none of the individual studies found evidence of clinical benefit with the use of folic acid medication in fragile X syndrome patients on any of the areas of interest, either psychological and learning capabilities or behaviour and social performance, as measured with standardised tools. "
4.	Anterior Temporal Lobectomy 10/01/2015 - "We have presented the case of a 24 year-old-man with fragile X syndrome who underwent successful left anterior temporal lobectomy for the treatment of medically refractory epilepsy who is now seizure free without further functional impairment. " 10/01/2015 - "We present the case of a 24-year-old man with medically refractory temporal lobe epilepsy and fragile X syndrome who underwent left anterior temporal lobectomy resulting in cessation of seizures. "
5.	Investigational Therapies (Experimental Therapy) 10/01/2001 - "[Experimental therapy: reactivation of the FMR1 gene involved in fragile X syndrome]."