Fragile X Tremor Ataxia Syndrome

An ataxia caused by expanded TRINUCLEOTIDE REPEATS in the FMR1 gene on the X chromosome. Occurs predominantly in men over 50 years of age. In addition to ataxia, TREMOR, brain atrophy, and DEMENTIA also occur. OMIM: 300623

Also Known As:

Networked: 310 relevant articles (5 outcomes, 31 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Ataxia (Dyssynergia)
2.	Fragile X Tremor Ataxia Syndrome
3.	Atrophy
4.	Tremor (Tremors)
5.	Cerebrovascular Disorders (Cerebrovascular Occlusion)

Experts

1.	Tassone, Flora: 59 articles (05/2022 - 07/2004)
2.	Hagerman, Randi J: 50 articles (05/2022 - 01/2004)
3.	Hagerman, Paul J: 44 articles (01/2021 - 01/2004)
4.	Willemsen, Rob: 27 articles (12/2021 - 10/2003)
5.	Todd, Peter K: 25 articles (12/2022 - 03/2010)
6.	Jin, Peng: 18 articles (01/2022 - 08/2007)
7.	Hagerman, Randi: 17 articles (01/2021 - 01/2006)
8.	Hall, Deborah A: 14 articles (12/2022 - 11/2005)
9.	Hukema, Renate K: 14 articles (12/2021 - 12/2008)
10.	Krans, Amy: 13 articles (01/2022 - 12/2010)

Drugs and Biologics

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

1.	Pregnanolone (Allopregnanolone)IBA 10/01/2017 - "Further studies are needed to verify the efficacy of allopregnanolone for treating FXTAS." 01/01/2021 - "A recent preliminary study reported that weekly infusions of Allopregnanolone (Allop) may improve deficits in executive function, learning and memory in FXTAS patients. " 01/01/2021 - "Allopregnanolone Improves Locomotor Activity and Arousal in the Aged CGG Knock-in Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome." 10/01/2017 - "The findings show the promise of allopregnanolone in improving cognitive functioning in patients with FXTAS and in partially alleviating some aspects of neurodegeneration. " 10/01/2017 - "Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome."
2.	TrehaloseIBA 09/30/2023 - "Trehalose consumption ameliorates pathogenesis in an inducible mouse model of the Fragile X-associated tremor/ataxia syndrome." 09/30/2023 - "Given the favorable safety profile of trehalose, it is promising to further explore the potential of this agent for early stage FXTAS." 09/30/2023 - "Here, we explored the effectiveness of nutritional trehalose supplementation in ameliorating symptoms in a mouse model of Fragile X-associated tremor/ataxia syndrome (FXTAS), an incurable late onset manifestation of moderately expanded trinucleotide CGG repeat expansion mutations in the 5' untranslated region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). "
3.	Varenicline (Chantix)FDA Link 02/01/2009 - "Treatment of imbalance with varenicline Chantix(R): report of a patient with fragile X tremor/ataxia syndrome." 02/01/2009 - "We describe the case of a man with Fragile X tremor/ataxia syndrome, whose ataxia and imbalance improved with the use of varenicline (Chantix) and reverted to baseline 10 days after varenicline was discontinued. "
4.	piperineIBA 01/01/2019 - "Moreover, piperine was also found to be effective for improving the r(CGG)exp associated splicing defects and RAN translation in a FXTAS cell model system. " 01/01/2019 - "Our results effectively provided the evidence that piperine strongly interacts with r(CGG)exp RNA and could be used as a suitable candidate for therapeutic development against FXTAS." 01/01/2019 - "Piperine Modulates Protein Mediated Toxicity in Fragile X-Associated Tremor/Ataxia Syndrome through Interacting Expanded CGG Repeat (r(CGG)exp) RNA."
5.	Biomarkers (Surrogate Marker)IBA 01/01/2021 - "The primary objective of this study was to investigate the correlation between longitudinal changes in the brain (area of the pons, midbrain, and MCP width) and the changes in the expression level of metabolic biomarkers of early diagnosis and progression of FXTAS in PM who, as part of an ongoing longitudinal study, emerged into two distinct categories. " 01/01/2020 - "Recent metabolic studies have shown novel findings in asymptomatic FMR1 premutation carriers and FXTAS, which provide promising insight through identification of potential biomarkers and therapeutic pathways. " 01/01/2020 - "The primary objective of this study was to investigate the alternative splicing landscape at the FMR1 locus in conjunction with brain measures in male individuals with a premutation allele enrolled in a very first longitudinal study, compared to age-matched healthy male controls, with the purpose of identifying biomarkers for early diagnosis, disease prediction and, a progression of FXTAS. " 12/01/2019 - "No biomarkers have yet been identified to allow early diagnosis of FXTAS, however, recent studies have reported subtle issues in the stability of younger premutation carriers, before disease onset. " 01/01/2018 - "Therefore, this study aimed to assess the utility of the Magnetic Resonance Parkinson Index (MRPI) as a potential MRI biomarker for FXTAS. "
6.	IronIBA 01/11/2023 - "Post hoc analysis confirmed PCA findings and further revealed increased iron content in the white matter, hippocampus, and amygdala in FXTAS cases than controls after adjusting for T2-hyperintensity ratings. " 01/11/2023 - "PCA of FXTAS cases revealed negative associations of T2-hyperintensity ratings with anatomic volumes and iron content in the white matter, hippocampus, and amygdala, that were independent from highly correlated number of regions with ICH and iron content in subcortical nuclei. " 01/01/2023 - "Post-hoc analysis confirmed PCA findings and further revealed increased iron content in the white matter, hippocampus and amygdala in FXTAS cases compared to controls, after adjusting for T2-hyperintensity ratings. " 01/01/2023 - "PCA of FXTAS cases revealed negative associations of T2-hyperintensity ratings with anatomic volumes and iron content in the white matter, hippocampus and amygdala, that were independent from a highly correlated number of regions with ICH and iron content in subcortical nuclei. " 01/01/2022 - "We estimated the prevalence of the MCP sign and pallidal T2-abnormalities in 230 male premutation carriers and 144 controls (aged 8-86), and examined the associations with FXTAS symptoms, CGG repeat length, and iron content in the cerebellar dentate nucleus and globus pallidus. "
7.	Messenger RNA (mRNA)IBA 12/01/2011 - "The current study utilizes structural magnetic resonance imaging (MRI) to examine the relationship between amygdala volume, CGG expansion size, FMR1 mRNA, and psychological symptoms in male premutation carriers without FXTAS compared with age and IQ matched controls. " 01/01/2021 - "Issues raised during genetic counseling related to risk for FXTAS associated with UFM and elevated FMR1 mRNA levels, as well as, reproductive options, with implications for future practice." 01/01/2020 - "Here we described 14 patients who had both lowered FMRP and elevated FMR1 mRNA levels, representing dual mechanisms of clinical involvement, which may combine features of both FXS and FXTAS. " 12/06/2019 - "Reduction of Fmr1 mRNA Levels Rescues Pathological Features in Cortical Neurons in a Model of FXTAS." 11/01/2017 - "Their characterization will also help to elucidating the mechanism(s) by which "toxic gain of function" of the FMR1 mRNA may play a role in FXTAS and/or in the other FMR1-associated conditions."
8.	RNA (Ribonucleic Acid)IBA 01/01/2014 - "In order to study the pathogenesis of FXTAS, new inducible transgenic mouse models have been developed that expresses either 11CGGs or 90CGGs at the RNA level under control of a Tet-On promoter. " 01/01/2023 - "Insights from RNA-sequencing data indicated that SUMOylation processes are significantly upregulated in FXTAS samples. " 01/01/2022 - "Finally, we demonstrate evidence that PSMB5 knockdown results in suppression of CGG neurotoxicity via both the RAN translation and RNA-mediated toxicity mechanisms, thereby presenting a therapeutic strategy for FXTAS." 01/01/2020 - "Both the gene and pathogenic trigger, a mutant expansion of CGG RNA, causing FXTAS are known. " 11/01/2018 - "Potential pathogenic mechanisms underlying Fragile X Tremor Ataxia Syndrome: RAN translation and/or RNA gain-of-function?"
9.	Memantine (Namenda)FDA Link 03/01/2014 - "This randomized, double-blind, placebo-controlled trial of memantine for individuals with FXTAS showed no benefit compared to placebo with respect to the selected outcome measures. " 03/01/2014 - "Memantine for fragile X-associated tremor/ataxia syndrome: a randomized, double-blind, placebo-controlled trial." 04/01/2020 - "To analyze placebo response from the first randomized controlled trial in FXTAS that evaluated cognitive and motor outcomes after 1 year of treatment with memantine. " 02/22/2016 - "These findings indicate that memantine may benefit attentional processes that represent fundamental components of executive function/dysfunction, thought to comprise the core cognitive deficit in FXTAS. " 02/22/2016 - "Memantine Improves Attentional Processes in Fragile X-Associated Tremor/Ataxia Syndrome: Electrophysiological Evidence from a Randomized Controlled Trial."
10.	5' Untranslated Regions (5' UTR)IBA 01/01/2019 - "Expansion of a CGG-repeat tract in the 5' UTR of FMR1 is responsible for the Fragile X-related disorders (FXDs), FXTAS, FXPOI and FXS. " 01/01/2018 - "The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5'UTR of FMR1. " 01/01/2014 - "FXTAS is caused by the presence of a long CGG repeat tract in the 5' UTR of the FMR1 gene. " 03/15/2013 - "Fragile X premutation-associated disorders, including Fragile X-associated Tremor Ataxia Syndrome, result from unmethylated CGG repeat expansions in the 5' untranslated region (UTR) of the FMR1 gene. " 08/16/2007 - "To test this hypothesis, we utilize a transgenic Drosophila model of FXTAS that expresses a premutation-length repeat (90 CGG repeats) from the 5' UTR of the human FMR1 gene and displays neuronal degeneration. "

Therapies and Procedures

1.	Therapeutics 12/01/2021 - "These data suggest that targeted small molecule therapy is effective in an FXTAS mouse model and has the potential to treat CGGexp-mediated diseases, including FXTAS." 09/01/2012 - "Our approach represents a unique isogenic, X-chromosomal epigenetic model to aid the development of targeted therapeutics for FXTAS, and more broadly as a model for the study of common neurodevelopmental (e.g. " 12/01/2011 - "A sample of patients was selected that participated in studies at two tertiary referral academic centres on the phenotype and therapy of FXTAS. " 03/01/2022 - "Taken together these findings, we addressed compound B1, B4, and B11 as potential lead molecules for developing promising therapeutics against FXTAS. " 02/15/2022 - "Hopefully, a better understanding of the molecular processes involved in the polymorphic features of FXTAS will lead to more specific and effective therapies for this complex disorder."
2.	Deep Brain Stimulation 07/01/2016 - "Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? " 03/01/2015 - "Long-term outcome of deep brain stimulation in fragile X-associated tremor/ataxia syndrome." 12/01/2014 - "Posterior subthalamic area deep brain stimulation for fragile X-associated tremor/ataxia syndrome." 04/01/2014 - "Which approach is better: bilateral versus unilateral thalamic deep brain stimulation in patients with fragile X-associated tremor ataxia syndrome." 05/01/2012 - "Treatment of fragile X-associated tremor/ataxia syndrome with unilateral deep brain stimulation."
3.	Precision Medicine 12/10/2022 - "ANN supports the prospect of an unbiased molecular definition in diagnosing FXTAS stages while identifying potential targets for personalized medicine." 10/01/2016 - "The use of antioxidants in the context of precision medicine is discussed with the goal of improving mitochondrial function in carriers with the potential of decreasing the morbidity and/or delaying FXTAS onset." 10/01/2016 - "Altered redox mitochondrial biology in the neurodegenerative disorder fragile X-tremor/ataxia syndrome: use of antioxidants in precision medicine." 05/01/2019 - "Based on this pilot study, allopregnanolone treatment has the potential for improving cognitive and GABA metabolism in FXTAS aligned with the concept of precision medicine."
4.	Palliative Care (Palliative Therapy) 10/01/2015 - "It is also prudent to recognize the imaging spectrum of metabolic, infective and autoimmune diseases with rapidly progressing dementia, such as methanol toxicity, central pontine myelinolysis (CPM), delayed post hypoxic leukoencephalopathy (DPHL), HIV, Creutzfeldt-Jakob Disease (CJD), Sjogren's syndrome, multiple sclerosis (MS), radiation necrosis and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), which are difficult to treat and often require palliative care. "
5.	Hysterectomy 09/30/2017 - "She is a carrier of the FMR1 premutation diagnosed by PCR and Southern Blot, complying with the clinical and radiological criteria of FXTAS, and in addition, has a history of vagal symptoms suggestive of ovarian failure and menstrual cycle disorders that led to hysterectomy at age 33 and was subsequently diagnosed with FXPOI. "