Anxiety-like behavior in Rett syndrome: characteristics and assessment by anxiety scales / K. V. BARNES in Journal of Neurodevelopmental Disorders, 7-1 (December 2015)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.30 Titre : Anxiety-like behavior in Rett syndrome: characteristics and assessment by anxiety scales Type de document : Texte imprimé et/ou numérique Auteurs : K. V. BARNES, Auteur ; F. R. COUGHLIN, Auteur ; H. M. O'LEARY, Auteur ; N. BRUCK, Auteur ; G. A. BAZIN, Auteur ; E. B. BEINECKE, Auteur ; A. C. WALCO, Auteur ; N. G. CANTWELL, Auteur ; W. E. KAUFMANN, Auteur Article en page(s) : p.30 Langues : Anglais (eng) Mots-clés : Anxiety  Intellectual disabilities  Problematic behavior  Rett syndrome  Social avoidance Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by regression of language and motor skills, cognitive impairment, and frequent seizures. Although the diagnostic criteria focus on communication, motor impairments, and hand stereotypies, behavioral abnormalities are a prevalent and disabling component of the RTT phenotype. Among these problematic behaviors, anxiety is a prominent symptom. While the introduction of the Rett Syndrome Behavioral Questionnaire (RSBQ) represented a major advancement in the field, no systematic characterization of anxious behavior using the RSBQ or other standardized measures has been reported. METHODS: This study examined the profiles of anxious behavior in a sample of 74 girls with RTT, with a focus on identifying the instrument with the best psychometric properties in this population. The parent-rated RSBQ, Anxiety, Depression, and Mood Scale (ADAMS), and Aberrant Behavior Checklist-Community (ABC-C), two instruments previously employed in children with neurodevelopmental disorders, were analyzed in terms of score profiles, relationship with age and clinical severity, reliability, concurrent validity, and functional implications. The latter were determined by regression analyses with the Vineland Adaptive Behavior Scales-Second Edition (Vineland-II) and the Child Health Questionnaire (CHQ), a quality of life measure validated in RTT. RESULTS: We found that scores on anxiety subscales were intermediate in range with respect to other behavioral constructs measured by the RSBQ, ADAMS, and ABC-C. Age did not affect scores, and severity of general anxiety was inversely correlated with clinical severity. We demonstrated that the internal consistency of the anxiety-related subscales were among the highest. Test-retest and intra-rater reliability was superior for the ADAMS subscales. Convergent and discriminant validity were measured by inter-scale correlations, which showed the best profile for the social anxiety subscales. Of these, only the ADAMS Social Avoidance showed correlation with quality of life. CONCLUSIONS: We conclude that anxiety-like behavior is a prominent component of RTT's behavioral phenotype, which affects predominantly children with less severe neurologic impairment and has functional consequences. Based on available data on standardized instruments, the ADAMS and in particular its Social Avoidance subscale has the best psychometric properties and functional correlates that make it suitable for clinical and research applications. En ligne : http://dx.doi.org/10.1186/s11689-015-9127-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Anxiety-like behavior in Rett syndrome: characteristics and assessment by anxiety scales [Texte imprimé et/ou numérique] / K. V. BARNES, Auteur ; F. R. COUGHLIN, Auteur ; H. M. O'LEARY, Auteur ; N. BRUCK, Auteur ; G. A. BAZIN, Auteur ; E. B. BEINECKE, Auteur ; A. C. WALCO, Auteur ; N. G. CANTWELL, Auteur ; W. E. KAUFMANN, Auteur . - p.30. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 7-1 (December 2015) . - p.30 Mots-clés : Anxiety  Intellectual disabilities  Problematic behavior  Rett syndrome  Social avoidance Index. décimale : PER Périodiques Résumé : BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by regression of language and motor skills, cognitive impairment, and frequent seizures. Although the diagnostic criteria focus on communication, motor impairments, and hand stereotypies, behavioral abnormalities are a prevalent and disabling component of the RTT phenotype. Among these problematic behaviors, anxiety is a prominent symptom. While the introduction of the Rett Syndrome Behavioral Questionnaire (RSBQ) represented a major advancement in the field, no systematic characterization of anxious behavior using the RSBQ or other standardized measures has been reported. METHODS: This study examined the profiles of anxious behavior in a sample of 74 girls with RTT, with a focus on identifying the instrument with the best psychometric properties in this population. The parent-rated RSBQ, Anxiety, Depression, and Mood Scale (ADAMS), and Aberrant Behavior Checklist-Community (ABC-C), two instruments previously employed in children with neurodevelopmental disorders, were analyzed in terms of score profiles, relationship with age and clinical severity, reliability, concurrent validity, and functional implications. The latter were determined by regression analyses with the Vineland Adaptive Behavior Scales-Second Edition (Vineland-II) and the Child Health Questionnaire (CHQ), a quality of life measure validated in RTT. RESULTS: We found that scores on anxiety subscales were intermediate in range with respect to other behavioral constructs measured by the RSBQ, ADAMS, and ABC-C. Age did not affect scores, and severity of general anxiety was inversely correlated with clinical severity. We demonstrated that the internal consistency of the anxiety-related subscales were among the highest. Test-retest and intra-rater reliability was superior for the ADAMS subscales. Convergent and discriminant validity were measured by inter-scale correlations, which showed the best profile for the social anxiety subscales. Of these, only the ADAMS Social Avoidance showed correlation with quality of life. CONCLUSIONS: We conclude that anxiety-like behavior is a prominent component of RTT's behavioral phenotype, which affects predominantly children with less severe neurologic impairment and has functional consequences. Based on available data on standardized instruments, the ADAMS and in particular its Social Avoidance subscale has the best psychometric properties and functional correlates that make it suitable for clinical and research applications. En ligne : http://dx.doi.org/10.1186/s11689-015-9127-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Arbaclofen in fragile X syndrome: results of phase 3 trials / Elizabeth BERRY-KRAVIS in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.3 Titre : Arbaclofen in fragile X syndrome: results of phase 3 trials Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth BERRY-KRAVIS, Auteur ; Randi J. HAGERMAN, Auteur ; J. VISOOTSAK, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; W. E. KAUFMANN, Auteur ; M. CHERUBINI, Auteur ; P. ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; P. WANG, Auteur ; Mark F. BEAR, Auteur ; Randall L. CARPENTER, Auteur Article en page(s) : p.3 Langues : Anglais (eng) Mots-clés : Arbaclofen  Fmr1  Fragile X syndrome  GABA agonist  Neurodevelopmental disorder  Targeted treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: Arbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study. The objective of the study is to determine safety and efficacy of arbaclofen for social avoidance in FXS. METHODS: Two phase 3 placebo-controlled trials were conducted, a flexible dose trial in subjects age 12-50 (209FX301, adolescent/adult study) and a fixed dose trial in subjects age 5-11 (209FX302, child study). The primary endpoint for both trials was the Social Avoidance subscale of the Aberrant Behavior Checklist-Community Edition, FXS-specific (ABC-CFX). Secondary outcomes included other ABC-CFX subscale scores, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), and Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Socialization domain score. RESULTS: A total 119 of 125 randomized subjects completed the adolescent/adult study (n = 57 arbaclofen, 62 placebo) and 159/172 completed the child study (arbaclofen 5 BID n = 38; 10 BID n = 39; 10 TID n = 38; placebo n = 44). There were no serious adverse events (AEs); the most common AEs included somatic (headache, vomiting, nausea), neurobehavioral (irritability/agitation, anxiety, hyperactivity), decreased appetite, and infectious conditions, many of which were also common on placebo. In the combined studies, there were 13 discontinuations (n = 12 arbaclofen, 1 placebo) due to AEs (all neurobehavioral). The adolescent/adult study did not show benefit for arbaclofen over placebo for any measure. In the child study, the highest dose group showed benefit over placebo on the ABC-CFX Irritability subscale (p = 0.03) and Parenting Stress Index (PSI, p = 0.03) and trends toward benefit on the ABC-CFX Social Avoidance and Hyperactivity subscales (both p < 0.1) and CGI-I (p = 0.119). Effect size in the highest dose group was similar to effect sizes for FDA-approved serotonin reuptake inhibitors (SSRIs). CONCLUSIONS: Arbaclofen did not meet the primary outcome of improved social avoidance in FXS in either study. Data from secondary measures in the child study suggests younger patients may derive benefit, but additional studies with a larger cohort on higher doses would be required to confirm this finding. The reported studies illustrate the challenges but represent a significant step forward in translating targeted treatments from preclinical models to clinical trials in humans with FXS. En ligne : http://dx.doi.org/10.1186/s11689-016-9181-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Arbaclofen in fragile X syndrome: results of phase 3 trials [Texte imprimé et/ou numérique] / Elizabeth BERRY-KRAVIS, Auteur ; Randi J. HAGERMAN, Auteur ; J. VISOOTSAK, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; W. E. KAUFMANN, Auteur ; M. CHERUBINI, Auteur ; P. ZAREVICS, Auteur ; Karen WALTON-BOWEN, Auteur ; P. WANG, Auteur ; Mark F. BEAR, Auteur ; Randall L. CARPENTER, Auteur . - p.3. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.3 Mots-clés : Arbaclofen  Fmr1  Fragile X syndrome  GABA agonist  Neurodevelopmental disorder  Targeted treatment Index. décimale : PER Périodiques Résumé : BACKGROUND: Arbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study. The objective of the study is to determine safety and efficacy of arbaclofen for social avoidance in FXS. METHODS: Two phase 3 placebo-controlled trials were conducted, a flexible dose trial in subjects age 12-50 (209FX301, adolescent/adult study) and a fixed dose trial in subjects age 5-11 (209FX302, child study). The primary endpoint for both trials was the Social Avoidance subscale of the Aberrant Behavior Checklist-Community Edition, FXS-specific (ABC-CFX). Secondary outcomes included other ABC-CFX subscale scores, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), and Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Socialization domain score. RESULTS: A total 119 of 125 randomized subjects completed the adolescent/adult study (n = 57 arbaclofen, 62 placebo) and 159/172 completed the child study (arbaclofen 5 BID n = 38; 10 BID n = 39; 10 TID n = 38; placebo n = 44). There were no serious adverse events (AEs); the most common AEs included somatic (headache, vomiting, nausea), neurobehavioral (irritability/agitation, anxiety, hyperactivity), decreased appetite, and infectious conditions, many of which were also common on placebo. In the combined studies, there were 13 discontinuations (n = 12 arbaclofen, 1 placebo) due to AEs (all neurobehavioral). The adolescent/adult study did not show benefit for arbaclofen over placebo for any measure. In the child study, the highest dose group showed benefit over placebo on the ABC-CFX Irritability subscale (p = 0.03) and Parenting Stress Index (PSI, p = 0.03) and trends toward benefit on the ABC-CFX Social Avoidance and Hyperactivity subscales (both p < 0.1) and CGI-I (p = 0.119). Effect size in the highest dose group was similar to effect sizes for FDA-approved serotonin reuptake inhibitors (SSRIs). CONCLUSIONS: Arbaclofen did not meet the primary outcome of improved social avoidance in FXS in either study. Data from secondary measures in the child study suggests younger patients may derive benefit, but additional studies with a larger cohort on higher doses would be required to confirm this finding. The reported studies illustrate the challenges but represent a significant step forward in translating targeted treatments from preclinical models to clinical trials in humans with FXS. En ligne : http://dx.doi.org/10.1186/s11689-016-9181-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Autistic behavior in boys with fragile X syndrome: social approach and HPA-axis dysfunction / J. E. ROBERTS in Journal of Neurodevelopmental Disorders, 1-4 (December 2009)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 1-4 (December 2009) . - p.283-91 Titre : Autistic behavior in boys with fragile X syndrome: social approach and HPA-axis dysfunction Type de document : Texte imprimé et/ou numérique Auteurs : J. E. ROBERTS, Auteur ; M. A. CLARKE, Auteur ; K. ALCORN, Auteur ; J. C. CARTER, Auteur ; A. C. LONG, Auteur ; W. E. KAUFMANN, Auteur Article en page(s) : p.283-91 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The primary goal of this study was to examine environmental and neuroendocrine factors that convey increased risk for elevated autistic behavior in boys with Fragile X syndrome (FXS). This study involves three related analyses: (1) examination of multiple dimensions of social approach behaviors and how they vary over time, (2) investigation of mean levels and modulation of salivary cortisol levels in response to social interaction, and (3) examination of the relationship of social approach and autistic behaviors to salivary cortisol. Poor social approach and elevated baseline and regulation cortisol are discernible traits that distinguish boys with FXS and ASD from boys with FXS only and from typically developing boys. In addition, blunted cortisol change is associated with increased severity of autistic behaviors only within the FXS and ASD group. Boys with FXS and ASD have distinct behavioral and neuroendocrine profiles that differentiate them from those with FXS alone and typically developing boys. En ligne : http://dx.doi.org/10.1007/s11689-009-9028-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342 [article] Autistic behavior in boys with fragile X syndrome: social approach and HPA-axis dysfunction [Texte imprimé et/ou numérique] / J. E. ROBERTS, Auteur ; M. A. CLARKE, Auteur ; K. ALCORN, Auteur ; J. C. CARTER, Auteur ; A. C. LONG, Auteur ; W. E. KAUFMANN, Auteur . - p.283-91. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 1-4 (December 2009) . - p.283-91 Index. décimale : PER Périodiques Résumé : The primary goal of this study was to examine environmental and neuroendocrine factors that convey increased risk for elevated autistic behavior in boys with Fragile X syndrome (FXS). This study involves three related analyses: (1) examination of multiple dimensions of social approach behaviors and how they vary over time, (2) investigation of mean levels and modulation of salivary cortisol levels in response to social interaction, and (3) examination of the relationship of social approach and autistic behaviors to salivary cortisol. Poor social approach and elevated baseline and regulation cortisol are discernible traits that distinguish boys with FXS and ASD from boys with FXS only and from typically developing boys. In addition, blunted cortisol change is associated with increased severity of autistic behaviors only within the FXS and ASD group. Boys with FXS and ASD have distinct behavioral and neuroendocrine profiles that differentiate them from those with FXS alone and typically developing boys. En ligne : http://dx.doi.org/10.1007/s11689-009-9028-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342

Developmental delay in Rett syndrome: data from the natural history study / J. L. NEUL in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.20 Titre : Developmental delay in Rett syndrome: data from the natural history study Type de document : Texte imprimé et/ou numérique Auteurs : J. L. NEUL, Auteur ; J. B. LANE, Auteur ; H. S. LEE, Auteur ; S. GEERTS, Auteur ; J. O. BARRISH, Auteur ; F. ANNESE, Auteur ; L. M. BAGGETT, Auteur ; K. BARNES, Auteur ; S. A. SKINNER, Auteur ; K. J. MOTIL, Auteur ; Daniel G. GLAZE, Auteur ; W. E. KAUFMANN, Auteur ; A. K. PERCY, Auteur Article en page(s) : p.20 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Early development appears normal in Rett syndrome (OMIM #312750) and may be more apparent than real. A major purpose of the Rett Syndrome (RTT) Natural History Study (NHS) was to examine achievement of developmental skills or abilities in classic and atypical RTT and assess phenotype-genotype relations in classic RTT. METHODS: Developmental skills in four realms, gross and fine motor, and receptive and expressive communication from initial enrollment and longitudinal assessments for up to 7 years, were assessed from 542 females meeting criteria for classic RTT and 96 females with atypical RTT divided into two groups: 50 with better and 46 with poorer functional scores. Data were analyzed for age at acquisition and loss of developmental features and for phenotype-genotype effects. Acquired, lost, and retained skills were compared between classic RTT and atypical RTT with better or poorer functional scores using Fisher's Exact test. To examine if the mean total score from the Motor Behavioral Assessment during follow-up differed for acquiring a skill, we used a generalized estimating equation assuming compound symmetry correlation structure within a subject. A general linear model was used to examine whether the mean age of acquisition or loss of a developmental skill differed by mutation type. P values <0.05 were considered significant and were two-sided without adjustment for multiple testing. Statistical analyses utilized SAS 9.3 (SAS Institute, Cary, NC, USA). RESULTS: Early developmental skills or abilities were often acquired albeit later than normal. More complex motor and communication acquisitions were delayed or absent. Clinical severity was less in those achieving the respective skill. Individuals with R133C, R294X, and R306C point mutations and 3' truncations tended to have better developmental outcomes. CONCLUSIONS: Early developmental skills were acquired by many, but clear differences from normal emerged, particularly in skills expected after age 6 months. When comparing clinical severity, greater acquisition of specific skills was associated with specific mutations, confirming the impression that these mutations confer milder developmental abnormalities. These data may serve for planning and interpretation of early intervention studies in RTT. TRIAL REGISTRATION: This NHS study, clinicaltrials.gov (NCT00296764), represents the largest group of RTT participants assessed repeatedly by direct examination. En ligne : http://dx.doi.org/10.1186/1866-1955-6-20 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346 [article] Developmental delay in Rett syndrome: data from the natural history study [Texte imprimé et/ou numérique] / J. L. NEUL, Auteur ; J. B. LANE, Auteur ; H. S. LEE, Auteur ; S. GEERTS, Auteur ; J. O. BARRISH, Auteur ; F. ANNESE, Auteur ; L. M. BAGGETT, Auteur ; K. BARNES, Auteur ; S. A. SKINNER, Auteur ; K. J. MOTIL, Auteur ; Daniel G. GLAZE, Auteur ; W. E. KAUFMANN, Auteur ; A. K. PERCY, Auteur . - p.20. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.20 Index. décimale : PER Périodiques Résumé : BACKGROUND: Early development appears normal in Rett syndrome (OMIM #312750) and may be more apparent than real. A major purpose of the Rett Syndrome (RTT) Natural History Study (NHS) was to examine achievement of developmental skills or abilities in classic and atypical RTT and assess phenotype-genotype relations in classic RTT. METHODS: Developmental skills in four realms, gross and fine motor, and receptive and expressive communication from initial enrollment and longitudinal assessments for up to 7 years, were assessed from 542 females meeting criteria for classic RTT and 96 females with atypical RTT divided into two groups: 50 with better and 46 with poorer functional scores. Data were analyzed for age at acquisition and loss of developmental features and for phenotype-genotype effects. Acquired, lost, and retained skills were compared between classic RTT and atypical RTT with better or poorer functional scores using Fisher's Exact test. To examine if the mean total score from the Motor Behavioral Assessment during follow-up differed for acquiring a skill, we used a generalized estimating equation assuming compound symmetry correlation structure within a subject. A general linear model was used to examine whether the mean age of acquisition or loss of a developmental skill differed by mutation type. P values <0.05 were considered significant and were two-sided without adjustment for multiple testing. Statistical analyses utilized SAS 9.3 (SAS Institute, Cary, NC, USA). RESULTS: Early developmental skills or abilities were often acquired albeit later than normal. More complex motor and communication acquisitions were delayed or absent. Clinical severity was less in those achieving the respective skill. Individuals with R133C, R294X, and R306C point mutations and 3' truncations tended to have better developmental outcomes. CONCLUSIONS: Early developmental skills were acquired by many, but clear differences from normal emerged, particularly in skills expected after age 6 months. When comparing clinical severity, greater acquisition of specific skills was associated with specific mutations, confirming the impression that these mutations confer milder developmental abnormalities. These data may serve for planning and interpretation of early intervention studies in RTT. TRIAL REGISTRATION: This NHS study, clinicaltrials.gov (NCT00296764), represents the largest group of RTT participants assessed repeatedly by direct examination. En ligne : http://dx.doi.org/10.1186/1866-1955-6-20 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346

Fragile X targeted pharmacotherapy: lessons learned and future directions / C. A. ERICKSON in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.7 Titre : Fragile X targeted pharmacotherapy: lessons learned and future directions Type de document : Texte imprimé et/ou numérique Auteurs : C. A. ERICKSON, Auteur ; M. H. DAVENPORT, Auteur ; T. L. SCHAEFER, Auteur ; L. K. WINK, Auteur ; Ernest V. PEDAPATI, Auteur ; J. A. SWEENEY, Auteur ; S. E. FITZPATRICK, Auteur ; W. Ted BROWN, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; Randi J. HAGERMAN, Auteur ; D. HESSL, Auteur ; W. E. KAUFMANN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur Article en page(s) : p.7 Langues : Anglais (eng) Mots-clés : Drug development  Fragile X syndrome  Genetic disorder  Targeted treatments  Translational treatment Index. décimale : PER Périodiques Résumé : Our understanding of fragile X syndrome (FXS) pathophysiology continues to improve and numerous potential drug targets have been identified. Yet, current prescribing practices are only symptom-based in order to manage difficult behaviors, as no drug to date is approved for the treatment of FXS. Drugs impacting a diversity of targets in the brain have been studied in recent FXS-specific clinical trials. While many drugs have focused on regulation of enhanced glutamatergic or deficient GABAergic neurotransmission, compounds studied have not been limited to these mechanisms. As a single-gene disorder, it was thought that FXS would have consistent drug targets that could be modulated with pharmacotherapy and lead to significant improvement. Unfortunately, despite promising results in FXS animal models, translational drug treatment development in FXS has largely failed. Future success in this field will depend on learning from past challenges to improve clinical trial design, choose appropriate outcome measures and age range choices, and find readily modulated drug targets. Even with many negative placebo-controlled study results, the field continues to move forward exploring both the new mechanistic drug approaches combined with ways to improve trial execution. This review summarizes the known phenotype and pathophysiology of FXS and past clinical trial rationale and results, and discusses current challenges facing the field and lessons from which to learn for future treatment development efforts. En ligne : http://dx.doi.org/10.1186/s11689-017-9186-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Fragile X targeted pharmacotherapy: lessons learned and future directions [Texte imprimé et/ou numérique] / C. A. ERICKSON, Auteur ; M. H. DAVENPORT, Auteur ; T. L. SCHAEFER, Auteur ; L. K. WINK, Auteur ; Ernest V. PEDAPATI, Auteur ; J. A. SWEENEY, Auteur ; S. E. FITZPATRICK, Auteur ; W. Ted BROWN, Auteur ; Dejan B. BUDIMIROVIC, Auteur ; Randi J. HAGERMAN, Auteur ; D. HESSL, Auteur ; W. E. KAUFMANN, Auteur ; Elizabeth BERRY-KRAVIS, Auteur . - p.7. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.7 Mots-clés : Drug development  Fragile X syndrome  Genetic disorder  Targeted treatments  Translational treatment Index. décimale : PER Périodiques Résumé : Our understanding of fragile X syndrome (FXS) pathophysiology continues to improve and numerous potential drug targets have been identified. Yet, current prescribing practices are only symptom-based in order to manage difficult behaviors, as no drug to date is approved for the treatment of FXS. Drugs impacting a diversity of targets in the brain have been studied in recent FXS-specific clinical trials. While many drugs have focused on regulation of enhanced glutamatergic or deficient GABAergic neurotransmission, compounds studied have not been limited to these mechanisms. As a single-gene disorder, it was thought that FXS would have consistent drug targets that could be modulated with pharmacotherapy and lead to significant improvement. Unfortunately, despite promising results in FXS animal models, translational drug treatment development in FXS has largely failed. Future success in this field will depend on learning from past challenges to improve clinical trial design, choose appropriate outcome measures and age range choices, and find readily modulated drug targets. Even with many negative placebo-controlled study results, the field continues to move forward exploring both the new mechanistic drug approaches combined with ways to improve trial execution. This review summarizes the known phenotype and pathophysiology of FXS and past clinical trial rationale and results, and discusses current challenges facing the field and lessons from which to learn for future treatment development efforts. En ligne : http://dx.doi.org/10.1186/s11689-017-9186-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Pharmacologic Interventions for Irritability, Aggression, Agitation and Self-Injurious Behavior in Fragile X Syndrome: An Initial Cross-Sectional Analysis / E. M. ECKERT in Journal of Autism and Developmental Disorders, 49-11 (November 2019)  

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Updated report on tools to measure outcomes of clinical trials in fragile X syndrome / Dejan B. BUDIMIROVIC in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

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