Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder / Andrew W. ZIMMERMAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 44 p. Titre : Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Andrew W. ZIMMERMAN, Auteur ; Kanwaljit SINGH, Auteur ; Susan L. CONNORS, Auteur ; Hua LIU, Auteur ; Anita A PANJWANI, Auteur ; Li-Ching LEE, Auteur ; Eileen DIGGINS, Auteur ; Ann FOLEY, Auteur ; Stepan MELNYK, Auteur ; Indrapal N. SINGH, Auteur ; S. Jill JAMES, Auteur ; Richard E. FRYE, Auteur ; Jed W. FAHEY, Auteur Article en page(s) : 44 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00451-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder [texte imprimé] / Andrew W. ZIMMERMAN, Auteur ; Kanwaljit SINGH, Auteur ; Susan L. CONNORS, Auteur ; Hua LIU, Auteur ; Anita A PANJWANI, Auteur ; Li-Ching LEE, Auteur ; Eileen DIGGINS, Auteur ; Ann FOLEY, Auteur ; Stepan MELNYK, Auteur ; Indrapal N. SINGH, Auteur ; S. Jill JAMES, Auteur ; Richard E. FRYE, Auteur ; Jed W. FAHEY, Auteur . - 44 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 44 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00451-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder / Andrew W. ZIMMERMAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 38 p. Titre : Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Andrew W. ZIMMERMAN, Auteur ; Kanwaljit SINGH, Auteur ; Susan L. CONNORS, Auteur ; Hua LIU, Auteur ; Anita A PANJWANI, Auteur ; Li-Ching LEE, Auteur ; Eileen DIGGINS, Auteur ; Ann FOLEY, Auteur ; Stepan MELNYK, Auteur ; Indrapal N. SINGH, Auteur ; S. Jill JAMES, Auteur ; Richard E. FRYE, Auteur ; Jed W. FAHEY, Auteur Article en page(s) : 38 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Biomarkers  Clinical trial  Placebo effects  Sulforaphane  defendants in matters related to pediatric neurology and Autism Spectrum Disorder.  JWF retired from the full-time faculty at Johns Hopkins in mid-2020, and now serves  as a scientific advisor to Brassica Protection Products LLC (Baltimore, MD, USA),  which produces a glucoraphanin-rich broccoli seed extract that it supplies to the  supplement industry. AWZ is named on a patent on the use of sulforaphane for the  treatment of autism that has been assigned to Johns Hopkins University. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. METHODS: We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3-12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. RESULTS: Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen's d 0.21; 95% CI - 0.46, 0.88 and 0.10; 95% CI - 0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen's d - 0.96; 95% CI - 1.73, - 0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p < 0.001). There were significant changes with SF compared to PL in biomarkers of glutathione redox status, mitochondrial respiration, inflammatory markers and heat shock proteins. Clinical laboratory studies confirmed product safety. SF was very well tolerated and side effects of treatment, none serious, included rare insomnia, irritability and intolerance of the taste and smell. LIMITATIONS: The sample size was limited to 45 children with ASD and we did not impute missing data. We were unable to document significant changes in clinical assessments during clinical visits in those taking SF compared to PL. The clinical results were confounded by placebo effects during the open-label phase. CONCLUSIONS: SF led to small yet non-statistically significant changes in the total and all subscale scores of the primary outcome measure, while for secondary outcome measures, caregivers' assessments of children taking SF showed statistically significant improvements compared to those taking PL on the ABC but not the SRS-2. Clinical effects of SF were less notable in children compared to our previous trial of a SF-rich preparation in young men with ASD. Several of the effects of SF on biomarkers correlated to clinical improvements. SF was very well tolerated and safe and effective based on our secondary clinical measures. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (NCT02561481) on September 28, 2015. Funding was provided by the U.S. Department of Defense. En ligne : http://dx.doi.org/10.1186/s13229-021-00447-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder [texte imprimé] / Andrew W. ZIMMERMAN, Auteur ; Kanwaljit SINGH, Auteur ; Susan L. CONNORS, Auteur ; Hua LIU, Auteur ; Anita A PANJWANI, Auteur ; Li-Ching LEE, Auteur ; Eileen DIGGINS, Auteur ; Ann FOLEY, Auteur ; Stepan MELNYK, Auteur ; Indrapal N. SINGH, Auteur ; S. Jill JAMES, Auteur ; Richard E. FRYE, Auteur ; Jed W. FAHEY, Auteur . - 38 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 38 p. Mots-clés : Autism spectrum disorder (ASD)  Biomarkers  Clinical trial  Placebo effects  Sulforaphane  defendants in matters related to pediatric neurology and Autism Spectrum Disorder.  JWF retired from the full-time faculty at Johns Hopkins in mid-2020, and now serves  as a scientific advisor to Brassica Protection Products LLC (Baltimore, MD, USA),  which produces a glucoraphanin-rich broccoli seed extract that it supplies to the  supplement industry. AWZ is named on a patent on the use of sulforaphane for the  treatment of autism that has been assigned to Johns Hopkins University. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. METHODS: We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3-12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. RESULTS: Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen's d 0.21; 95% CI - 0.46, 0.88 and 0.10; 95% CI - 0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen's d - 0.96; 95% CI - 1.73, - 0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p < 0.001). There were significant changes with SF compared to PL in biomarkers of glutathione redox status, mitochondrial respiration, inflammatory markers and heat shock proteins. Clinical laboratory studies confirmed product safety. SF was very well tolerated and side effects of treatment, none serious, included rare insomnia, irritability and intolerance of the taste and smell. LIMITATIONS: The sample size was limited to 45 children with ASD and we did not impute missing data. We were unable to document significant changes in clinical assessments during clinical visits in those taking SF compared to PL. The clinical results were confounded by placebo effects during the open-label phase. CONCLUSIONS: SF led to small yet non-statistically significant changes in the total and all subscale scores of the primary outcome measure, while for secondary outcome measures, caregivers' assessments of children taking SF showed statistically significant improvements compared to those taking PL on the ABC but not the SRS-2. Clinical effects of SF were less notable in children compared to our previous trial of a SF-rich preparation in young men with ASD. Several of the effects of SF on biomarkers correlated to clinical improvements. SF was very well tolerated and safe and effective based on our secondary clinical measures. TRIAL REGISTRATION: This study was prospectively registered at clinicaltrials.gov (NCT02561481) on September 28, 2015. Funding was provided by the U.S. Department of Defense. En ligne : http://dx.doi.org/10.1186/s13229-021-00447-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

The feasibility and utility of hair follicle sampling to measure FMRP and FMR1 mRNA in children with or without fragile X syndrome: a pilot study / Isha JALNAPURKAR in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : The feasibility and utility of hair follicle sampling to measure FMRP and FMR1 mRNA in children with or without fragile X syndrome: a pilot study Type de document : texte imprimé Auteurs : Isha JALNAPURKAR, Auteur ; Jean A. FRAZIER, Auteur ; Mark ROTH, Auteur ; David M. COCHRAN, Auteur ; Ann FOLEY, Auteur ; Taylor MERK, Auteur ; Lauren VENUTI, Auteur ; Lucienne RONCO, Auteur ; Shane RAINES, Auteur ; Diego CADAVID, Auteur Langues : Anglais (eng) Mots-clés : Male  Humans  Fragile X Syndrome/genetics  Fragile X Mental Retardation Protein/genetics  RNA, Messenger/genetics/metabolism  Hair Follicle/metabolism  Pilot Projects  Clinical biomarker  FMR1 mRNA  Fmrp  Fragile X  Hair follicle  during the experimental work and writing of the manuscript. They are no longer  with Fulcrum Therapeutics, but they own equity in Fulcrum Therapeutics. D. C. and  M. R. are currently full-time employees of X4 Pharmaceuticals, which is not  related to this work. J. A. F. receives research support from Healx, Tetra, and  Quadrant. D. M. C. consults with Abbvie Inc. The other authors declare that they  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (> 200 base pairs) on the promotor region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, fragile X messenger ribonucleoprotein 1 (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this, it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 mRNA and FMRP. METHODS: Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules. RESULTS: There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants and lowest in the FXS boys. Measurement of FMR1 mRNA and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab. CONCLUSION: Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home, and office settings, is feasible, repeatable, and can be used for measurement of FMR1 mRNA and FMRP in longitudinal studies. En ligne : https://dx.doi.org/10.1186/s11689-022-09465-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] The feasibility and utility of hair follicle sampling to measure FMRP and FMR1 mRNA in children with or without fragile X syndrome: a pilot study [texte imprimé] / Isha JALNAPURKAR, Auteur ; Jean A. FRAZIER, Auteur ; Mark ROTH, Auteur ; David M. COCHRAN, Auteur ; Ann FOLEY, Auteur ; Taylor MERK, Auteur ; Lauren VENUTI, Auteur ; Lucienne RONCO, Auteur ; Shane RAINES, Auteur ; Diego CADAVID, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Male  Humans  Fragile X Syndrome/genetics  Fragile X Mental Retardation Protein/genetics  RNA, Messenger/genetics/metabolism  Hair Follicle/metabolism  Pilot Projects  Clinical biomarker  FMR1 mRNA  Fmrp  Fragile X  Hair follicle  during the experimental work and writing of the manuscript. They are no longer  with Fulcrum Therapeutics, but they own equity in Fulcrum Therapeutics. D. C. and  M. R. are currently full-time employees of X4 Pharmaceuticals, which is not  related to this work. J. A. F. receives research support from Healx, Tetra, and  Quadrant. D. M. C. consults with Abbvie Inc. The other authors declare that they  have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat (> 200 base pairs) on the promotor region of the fragile X messenger ribonucleoprotein 1 gene (FMR1). This leads to the deficiency or absence of the encoded protein, fragile X messenger ribonucleoprotein 1 (FMRP). FMRP has a central role in the translation of mRNAs involved in synaptic connections and plasticity. Recent studies have demonstrated the benefit of therapeutics focused on reactivation of the FMR1 locus towards improving key clinical phenotypes via restoration of FMRP and ultimately disease modification. A key step in future studies directed towards this effort is the establishment of proof of concept (POC) for FMRP reactivation in individuals with FXS. For this, it is key to determine the feasibility of repeated collection of tissues or fluids to measure FMR1 mRNA and FMRP. METHODS: Individuals, ages 3 to 22 years of age, with FXS and those who were typically developing participated in this single-site pilot clinical biomarker study. The repeated collection of hair follicles was compared with the collection of blood and buccal swabs for detection of FMR1 mRNA and FMRP and related molecules. RESULTS: There were n = 15 participants, of whom 10 had a diagnosis of FXS (7.0 ± 3.56 years) and 5 were typically developing (8.2 ± 2.77 years). Absolute levels of FMRP and FMR1 mRNA were substantially higher in healthy participants compared to full mutation and mosaic FXS participants and lowest in the FXS boys. Measurement of FMR1 mRNA and FMRP levels by any method did not show any notable variation by collection location at home versus office across the various sample collection methodologies of hair follicle, blood sample, and buccal swab. CONCLUSION: Findings demonstrated that repeated sampling of hair follicles in individuals with FXS, in both, home, and office settings, is feasible, repeatable, and can be used for measurement of FMR1 mRNA and FMRP in longitudinal studies. En ligne : https://dx.doi.org/10.1186/s11689-022-09465-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

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