A double-blind, randomized, placebo-controlled clinical study of trofinetide in the treatment of fragile X syndrome

Berry-Kravis, Elizabeth; Horrigan, Joseph P.; Tartaglia, Nicole; Hagerman, Randi; Kolevzon, Alexander; Erickson, Craig A.; Hatti, Shivkumar; Snape, Mike; Yaroshinsky, Alex; Stoms, George; Sanders, Kevin; Frazier, Jean; Challman, Thomas; Innis, Jeffrey; King, Bryan; Cubells, Joseph; Visootsak, Jeannie; Skinner, Steven; Treadwell-Deering, Dianne; Vinson, Sherry Sellers; Needelman, Howard; Glass, Larry; Jones, Nancy E.

doi:10.1016/j.pediatrneurol.2020.04.019

Cited by 102Genetics and Neurodevelopmental DisordersAlzheimer's disease research and treatmentsAutism Spectrum Disorder Research

A double-blind, randomized, placebo-controlled clinical study of trofinetide in the treatment of fragile X syndrome

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Berry-Kravis, Elizabeth, Horrigan, Joseph P., Tartaglia, Nicole, Hagerman, Randi, Kolevzon, Alexander, Erickson, Craig A., Hatti, Shivkumar, Snape, Mike +15 more·2020·Pediatric Neurology

DOI 10.1016/j.pediatrneurol.2020.04.019

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Abstract

BACKGROUND: We analyze the safety and tolerability of trofinetide and provide a preliminary evaluation of its efficacy in adolescent and adult males with fragile X syndrome. METHODS: This study was an exploratory, phase 2, multicenter, double-blind, placebo-controlled, parallel group study of the safety and tolerability of orally administered trofinetide in 72 adolescent and adult males with fragile X syndrome. Subjects were randomly assigned in a 1:1:1 ratio to 35 or 70 mg/kg twice daily trofinetide or placebo for 28 days. Safety assessments included adverse events, clinical laboratory tests, vital signs, electrocardiograms, physical examinations, and concomitant medications. Efficacy measurements were categorized into four efficacy domains, which related to clinically relevant phenotypic dimensions of impairment associated with fragile X syndrome. RESULTS: Both 35 and 70 mg/kg dose levels of trofinetide were well tolerated and appeared to be generally safe. Trofinetide at the 70 mg/kg dose level demonstrated efficacy compared with placebo based on prespecified criteria. On the basis of a permutation test, the probability of a false-positive outcome for the achieved prespecified success was 0.045. In the group analysis, improvement from treatment baseline was demonstrated on three fragile X syndrome-specific outcome measures. CONCLUSIONS: Trofinetide was well tolerated in adolescent and adult males with fragile X syndrome. Despite the relatively short duration of the study, a consistent signal of efficacy at the higher dose was observed in both caregiver and clinician assessments, based on a novel analytical model incorporating evaluation of multiple key symptom areas of fragile X syndrome. This finding suggests a potential for trofinetide treatment to provide clinically meaningful improvement in core fragile X syndrome symptoms.

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In a 28-day controlled trial in adolescent and adult patients with FXS, trofinetide 70 mg/kg/day was significantly beneficial compared to placebo on the primary components of the Fragile X Syndrome Rating Scale, a Fragile X Specific Domain Scale, and the ABCFX.
“Results demonstrated that the 70 mg/kg/day was significantly beneficial compared to placebo with a permutation test utilizing the primary components of the Fragile X Syndrome Rating Scale, a Fragile X Specific Domain Scale on a visual analogue format, and the ABCFX.”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [138]

Selective publication of antidepressant trials and its influence on apparent efficacy
Turner, E. H., Matthews, A. M., Linardatos, E., Tell, R. A., & Rosenthal, R. (2008) · New England Journal of Medicine · doi:10.1056/nejmsa065779 · Cited by 2,435 · see citing works
A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: Report of 35 cases
Hagberg, B. A., Aicardi, J. F., Dias, K., & Ramos, O. (1983) · Annals of Neurology · doi:10.1002/ana.410140412 · Cited by 1,515 · see citing works
Rett syndrome: Revised diagnostic criteria and nomenclature
Neul, J. L., Kaufmann, W. E., Glaze, D. G., Christodoulou, J., Clarke, A. J., Bahi‐Buisson, N., Leonard, H., Bailey, M. E. S., Schanen, N. C., Zappella, M., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22124 · Cited by 1,398 · see citing works
Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): A Phase 2 Trial of Intracoronary Gene Therapy of Sarcoplasmic Reticulum Ca 2+ -ATPase in Patients With Advanced Heart Failure
Jessup, M., Greenberg, B., Mancini, D., Cappola, T., Pauly, D. F., Jaski, B., Yaroshinsky, A., Zsebo, K. M., Dittrich, H., & Hajjar, R. J. (2011) · Circulation · doi:10.1161/circulationaha.111.022889 · Cited by 760 · see citing works
Self-citation
Dendritic Spine Structural Anomalies in Fragile-X Mental Retardation Syndrome
Irwin, S. A. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.10.1038 · Cited by 626 · see citing works
Advances in the Treatment of Fragile X Syndrome
Hagerman, R. J., Berry-Kravis, E., Kaufmann, W. E., Ono, M. Y., Tartaglia, N., Lachiewicz, A., Kronk, R., Delahunty, C., Hessl, D., Visootsak, J., et al. (2009) · Pediatrics · doi:10.1542/peds.2008-0317 · Cited by 596 · see citing works
Self-citation
Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice
Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., McCurry, C., Fu, D. D., Flannery, R., Jaenisch, R., & Sur, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812394106 · Cited by 593 · see citing works
Regulation of Dendritic Morphogenesis by Ras–PI3K–Akt–mTOR and Ras–MAPK Signaling Pathways
Kumar, V., Zhang, M.-X., Swank, M. W., Kunz, J., & Wu, G.-Y. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2284-05.2005 · Cited by 588 · see citing works
Abnormal Development of Dendritic Spines inFMR1Knock-Out Mice
Nimchinsky, E. A., Oberlander, A. M., & Svoboda, K. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05139.2001 · Cited by 560 · see citing works
Dysregulation of mTOR signaling in fragile X syndrome
Sharma, A., Hoeffer, C. A., Takayasu, Y., Miyawaki, T., McBride, S. M., Klann, E., & Zukin, R. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3696-09.2010 · Cited by 557 · see citing works
Specific mutations in Methyl-CpG-Binding Protein 2 confer different severity in Rett syndrome
Neul, J. L., Fang, P., Barrish, J., Lane, J., Caeg, E. B., Smith, E. O., Zoghbi, H., Percy, A., & Glaze, D. G. (2008) · Neurology · doi:10.1212/01.wnl.0000291011.54508.aa · Cited by 498 · see citing works
Psychometric characteristics of the aberrant behavior checklist.
Aman, M. G., Singh, N. N., Stewart, A. W., & Field, C. J. (1985) · PubMed · Cited by 458 · see citing works
Co‐occurring conditions associated with FMR1 gene variations: Findings from a national parent survey
Bailey, D. B., Raspa, M., Olmsted, M. G., & Holiday, D. B. (2008) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32439 · Cited by 445 · see citing works
Incidence of Fragile X Syndrome by Newborn Screening for Methylated FMR1 DNA
Coffee, B., Keith, K., Albizua, I., Malone, T., Mowrey, J., Sherman, S. L., & Warren, S. T. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.09.007 · Cited by 436 · see citing works
Autism Spectrum Phenotype in Males and Females with Fragile X Full Mutation and Premutation
Clifford, S. M., Dissanayake, C., Bui, M., Huggins, R., Taylor, A. K., & Loesch, D. Z. (2006) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-006-0205-z · Cited by 380 · see citing works
Rett syndrome in Australia: A review of the epidemiology
Laurvick, C. L., de Klerk, N. H., Bower, C. I., Christodoulou, J., Ravine, D., Ellaway, C., Williamson, S. L., & Leonard, H. (2006) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2005.10.037 · Cited by 340 · see citing works
Parent-Defined Target Symptoms Respond to Risperidone in RUPP Autism Study: Customer Approach to Clinical Trials
ARNOLD, L. E., VITIELLO, B., MCDOUGLE, C., SCAHILL, L., SHAH, B., GONZALEZ, N. M., CHUANG, S., DAVIES, M., HOLLWAY, J., AMAN, M. G., et al. (2003) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200312000-00011 · Cited by 218 · see citing works
Measuring social communication behaviors as a treatment endpoint in individuals with autism spectrum disorder
Anagnostou, E., Jones, N., Huerta, M., Halladay, A. K., Wang, P., Scahill, L., Horrigan, J. P., Kasari, C., Lord, C., Choi, D., et al. (2015) · Autism · doi:10.1177/1362361314542955 · Cited by 210 · see citing works
Self-citation
Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome
Hoeffer, C. A., Sanchez, E., Hagerman, R. J., Mu, Y., Nguyen, D. V., Wong, H., Whelan, A. M., Zukin, R. S., Klann, E., & Tassone, F. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00768.x · Cited by 198 · see citing works
Self-citation
Psychometric Study of the Aberrant Behavior Checklist in Fragile X Syndrome and Implications for Targeted Treatment
Sansone, S. M., Widaman, K. F., Hall, S. S., Reiss, A. L., Lightbody, A. A., Kaufmann, W. E., Berry‐Kravis, E., Lachiewicz, A. M., Brown, E. C., & Hessl, D. R. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1370-2 · Cited by 177 · see citing works
Self-citation
Astrocytes prevent abnormal neuronal development in the fragile X mouse.
Jacobs, S., & Doering, L. C. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5027-09.2010 · Cited by 170 · see citing works
Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome
Glaze, D. G., Neul, J. L., Kaufmann, W. E., Berry-Kravis, E., Condon, S., Stoms, G., Oosterholt, S., Della Pasqua, O., Glass, L., Jones, N. E., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000007316 · Cited by 160 · see citing works
Self-citation
Developmental delay in Rett syndrome: data from the natural history study
Neul, J. L., Lane, J. B., Lee, H. S., Geerts, S. P., Barrish, J. O., Annese, F., Baggett, L., Barnes, K., Skinner, S. A., Motil, K. J., et al. (2014) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-6-20 · Cited by 159 · see citing works
Self-citation
Rett syndrome: analysis of deaths in the British survey.
Kerr, A., Armstrong, D. D., Prescott, R. J., Doyle, D., & Kearney, D. L. (1997) · PubMed · Cited by 159 · see citing works
Updated report on tools to measure outcomes of clinical trials in fragile X syndrome
Budimirovic, D. B., Berry‐Kravis, E., Erickson, C. A., Hall, S. S., Hessl, D. R., Reiss, A. L., King, M. K., Abbeduto, L., & Kaufmann, W. E. (2017) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-017-9193-x · Cited by 157 · see citing works
Self-citation
Outcome Measures for Clinical Trials in Fragile X Syndrome
Berry‐Kravis, E., Hessl, D. R., Abbeduto, L., Reiss, A. L., Beckel-Mitchener, A. C., & Urv, T. K. (2013) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e31829d1f20 · Cited by 154 · see citing works
Self-citation
Rett syndrome diagnostic criteria: Lessons from the Natural History Study
Percy, A. K., Neul, J. L., Glaze, D. G., Motil, K. J., Skinner, S. A., Khwaja, O., Lee, H., Lane, J. B., Barrish, J. O., Annese, F., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22154 · Cited by 144 · see citing works
Self-citation
A fragile balance: FMR1 expression levels
Oostra, B. A., & Willemsen, R. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg298 · Cited by 128 · see citing works
Recent advances in MeCP2 structure and functionThis paper is one of a selection of papers published in this Special Issue, entitled 29th Annual International Asilomar Chromatin and Chromosomes Conference, and has undergone the Journal’s usual peer review process.
Hite, K. C., Adams, V. H., & Hansen, J. C. (2009) · Biochemistry and Cell Biology · doi:10.1139/o08-115 · Cited by 127 · see citing works
Rett syndrome and associated movement disorders
FitzGerald, P. M., Jankovic, J. J., & Percy, A. K. (1990) · Movement Disorders · doi:10.1002/mds.870050303 · Cited by 125 · see citing works
DNA methylation and Rett syndrome
Kriaučionis, S., & Bird, A. P. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg286 · Cited by 125 · see citing works
The Changing Face of Survival in Rett Syndrome and MECP2-Related Disorders
Tarquinio, D. C., Hou, W., Neul, J. L., Kaufmann, W. E., Glaze, D. G., Motil, K. J., Skinner, S. A., Lee, H. S., & Percy, A. K. (2015) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2015.06.003 · Cited by 124 · see citing works
Self-citation
Longevity in Rett Syndrome: Analysis of the North American Database
Kirby, R. S., Lane, J. B., Childers, J., Skinner, S. A., Annese, F., Barrish, J. O., Glaze, D. G., MacLeod, P., & Percy, A. K. (2009) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2009.07.015 · Cited by 106 · see citing works
Self-citation
A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome
Glaze, D. G., Neul, J. L., Percy, A. K., Feyma, T. J., Beisang, A., Yaroshinsky, A., Stoms, G. B., Zuchero, D., Horrigan, J. P., Glass, L., et al. (2017) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2017.07.002 · Cited by 104 · see citing works
Self-citation
High male:female ratio of germ-line mutations: an alternative explanation for postulated gestational lethality in males in X-linked dominant disorders.
Thomas, G. H. (1996) · PubMed · Cited by 89 · see citing works
Improving Treatment Trial Outcomes for Rett Syndrome
Neul, J. L., Glaze, D. G., Percy, A. K., Feyma, T. J., Beisang, A., Dinh, T., Suter, B., Anagnostou, E. A., Snape, M., Horrigan, J. P., et al. (2015) · Journal of Child Neurology · doi:10.1177/0883073815579707 · Cited by 85 · see citing works
Self-citation
NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats
Wei, H. H., Lu, X. M., Shear, D. A., Waghray, A., Yao, C., Tortella, F. C., & Dave, J. R. (2009) · Journal of Neuroinflammation · doi:10.1186/1742-2094-6-19 · Cited by 80 · see citing works
NNZ-2566, a novel analog of (1–3) IGF-1, as a potential therapeutic agent for fragile X syndrome
Deacon, R. M. J., Glass, L., Snape, M., Hurley, M. J., Altimiras, F. J., Biekofsky, R. R., & Cogram, P. (2015) · NeuroMolecular Medicine · doi:10.1007/s12017-015-8341-2 · Cited by 78 · see citing works
Self-citation
Aberrant behaviors of young boys with fragile X syndrome.
Am, L., Ga, S., Cm, G., Sn, R., & Rao, K. (1994) · PubMed · Cited by 71 · see citing works
Difference, significant difference and clinically meaningful difference: The meaning of change in rehabilitation
Dvir, Z. (2015) · Journal of Exercise Rehabilitation · doi:10.12965/jer.150199 · Cited by 64 · see citing works
The Incidence of Rett Syndrome in France
Bienvenu, T., Philippe, C., de Roux, N., Raynaud, M., Bonnefont, J., Pasquier, L., Lesca, G., Mancini, J., Jonveaux, P., Moncla, A., et al. (2006) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2005.10.013 · Cited by 57 · see citing works
Distribution-based estimates of clinically significant changes in the International Standards for Neurological Classification of Spinal Cord Injury motor and sensory scores.
Scivoletto, G., Tamburella, F., Laurenza, L., & Molinari, M. (2013) · PubMed · Cited by 45 · see citing works
Contaminated and Unusual Food Combinations: What Do People With Prader-Willi Syndrome Choose?
Dykens, E. M. (2000) · Mental Retardation · doi:10.1352/0047-6765(2000)038 · Cited by 42 · see citing works
Mechanism of Action for NNZ-2566 Anti-inflammatory Effects Following PBBI Involves Upregulation of Immunomodulator ATF3
Cartagena, C. M., Phillips, K. L., Williams, G. L., Konopko, M. A., Tortella, F. C., Dave, J. R., & Schmid, K. E. (2013) · NeuroMolecular Medicine · doi:10.1007/s12017-013-8236-z · Cited by 36 · see citing works
Fragile X syndrome. Molecular and clinical insights and treatment issues.
Hagerman, R. J. (1997) · Europe PMC (PubMed Central) · Cited by 34 · see citing works
Self-citation
NNZ-2566, a Glypromate Analog, Attenuates Brain Ischemia-Induced Non-Convulsive Seizures in Rats
Lu, X. M., Si, Y., Williams, A. J., Hartings, J. A., Gryder, D. S., & Tortella, F. C. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.109 · Cited by 34 · see citing works
Aging in Persons with Rett Syndrome: An Updated Review
Lotan, M., Merrick, J., Kandel, I., & Morad, M. (2010) · The Scientific World JOURNAL · doi:10.1100/tsw.2010.79 · Cited by 20 · see citing works
Prevalence study of Rett syndrome in North Dakota children
Burd, L., Vesley, B., Martsolf, J. T., & Kerbeshian, J. (1991) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320380414 · Cited by 18 · see citing works
Rett Syndrome: Coming to Terms with Treatment
Percy, A. K. (2014) · Advances in Neuroscience · doi:10.1155/2014/345270 · Cited by 17 · see citing works
Robust inference from multiple test statistics via permutations: a better alternative to the single test statistic approach for randomized trials
Ganju, J., Yu, X., & Ma, G. (2013) · Pharmaceutical Statistics · doi:10.1002/pst.1582 · Cited by 14 · see citing works

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Saby, J. N., Peters, S. U., Roberts, T. P. L., Nelson, C. A., & Marsh, E. D. (2020) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2020.00030 · Cited by 45 · see citing works
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Raspa, M., Bann, C., Gwaltney, A. Y., Benke, T. A., Fu, C., Glaze, D. G., Haas, R., Heydemann, P. T., Jones, M. D., Kaufmann, W. E., et al. (2020) · American Journal on Intellectual and Developmental Disabilities · doi:10.1352/1944-7558-125.6.493 · Cited by 44 · see citing works
Self-citation
Key issues in Rett syndrome: emotional, behavioural and autonomic dysregulation (EBAD) - a target for clinical trials
Singh, J., & Santosh, P. (2018) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-018-0873-8 · Cited by 40 · see citing works
Metabolic Signatures Differentiate Rett Syndrome From Unaffected Siblings
Neul, J. L., Skinner, S. A., Annese, F., Lane, J. B., Heydemann, P. T., Jones, M. D., Kaufmann, W. E., Glaze, D. G., & Percy, A. K. (2020) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2020.00007 · Cited by 39 · see citing works
Self-citation
Response to Placebo in Fragile X Syndrome Clinical Trials: An Initial Analysis
Luu, S., Province, H. S., Berry‐Kravis, E., Hagerman, R. J., Hessl, D. R., Vaidya, D. M., Lozano, R., Rosselot, H., Erickson, C. A., Kaufmann, W. E., et al. (2020) · Brain Sciences · doi:10.3390/brainsci10090629 · Cited by 40 · see citing works
Self-citation
Emerging Gene and Small Molecule Therapies for the Neurodevelopmental Disorder Angelman Syndrome
Copping, N. A., McTighe, S. M., Fink, K. D., & Silverman, J. L. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01082-x · Cited by 39 · see citing works
Rett Syndrome: The Emerging Landscape of Treatment Strategies
Percy, A. K., Ananth, A., & Neul, J. L. (2024) · CNS Drugs · doi:10.1007/s40263-024-01106-y · Cited by 36 · see citing works
Breathing disturbances in Rett syndrome
Ramirez, J., Karlen‐Amarante, M., Wang, J.-D. J., Huff, A. D., & Burgraff, N. J. (2022) · Handbook of clinical neurology · doi:10.1016/b978-0-323-91532-8.00018-5 · Cited by 34 · see citing works
Trofinetide for Rett Syndrome: Highlights on the Development and Related Inventions of the First USFDA-Approved Treatment for Rare Pediatric Unmet Medical Need
Hudu, S. A., El-Migdadi, F., Al-Qtaitat, A., Almehmadi, M. M., Alsaiari, A. A., Allahyani, M. A., Aljuaid, A., Salih, M. M., Alghamdi, A., Alrofaidi, M. A., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12155114 · Cited by 32 · see citing works
Pharmacological read-through of R294X Mecp2 in a novel mouse model of Rett syndrome
Merritt, J. K., Collins, B. E., Erickson, K. R., Dong, H., & Neul, J. L. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa102 · Cited by 29 · see citing works
Clinical trials for Lennox–Gastaut syndrome: Challenges and priorities
Knowles, J. K., Warren, A. E. L., Mohamed, I., Stafstrom, C. E., Koh, H. Y., Samanta, D., Shellhaas, R. A., Gupta, G., Dixon‐Salazar, T., Tran, L., et al. (2024) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.52211 · Cited by 28 · see citing works
Rett syndrome from bench to bedside: recent advances
Ehinger, Y., Matagne, V., Villard, L., & Roux, J. (2018) · F1000Research · doi:10.12688/f1000research.14056.1 · Cited by 28 · see citing works
Criss‐crossing autism spectrum disorder and adult neurogenesis
Bicker, F., Nardi, L., Maier, J., Vasić, V., & Schmeisser, M. J. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15501 · Cited by 20 · see citing works
Biochemical mechanisms in pathogenesis of infantile epileptic spasm syndrome
Riikonen, R. (2023) · Seizure · doi:10.1016/j.seizure.2023.01.004 · Cited by 26 · see citing works
Safety and efficacy of genetic MECP2 supplementation in the R294X mouse model of Rett syndrome
Collins, B. E., Merritt, J. K., Erickson, K. R., & Neul, J. L. (2021) · Genes Brain & Behavior · doi:10.1111/gbb.12739 · Cited by 24 · see citing works
Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions
Bach, S., Shovlin, S., Moriarty, M. J., Bardoni, B., & Tropea, D. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.764761 · Cited by 23 · see citing works
A Coordinated Attack: Rett Syndrome Therapeutic Development
Gogliotti, R. G., & Niswender, C. M. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.02.007 · Cited by 21 · see citing works
What a finding of gene copy number variation can add to the diagnosis of developmental neuropsychiatric disorders
Vorstman, J. A. S., & Scherer, S. W. (2021) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.12.017 · Cited by 19 · see citing works
A Phase 1, Open-Label Study to Evaluate the Effects of Food and Evening Dosing on the Pharmacokinetics of Oral Trofinetide in Healthy Adult Subjects
Darwish, M., Youakim, J. M., Harlick, J., DeKarske, D., & Stankovic, S. (2022) · Clinical Drug Investigation · doi:10.1007/s40261-022-01156-4 · Cited by 21 · see citing works
Concise Overview of Glypromate Neuropeptide Research: From Chemistry to Pharmacological Applications in Neurosciences
Silva-Reis, S. C., Sampaio‐Dias, I. E., Costa, V. M., Correia, X. C., Costa-Almeida, H. F., Xerardo Garcia-mera, B., & Rodríguez-Borges, J. E. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00675 · Cited by 21 · see citing works
Improving clinical trial readiness to accelerate development of new therapeutics for Rett syndrome
Leonard, H., Gold, W. A., Samaco, R. C., Şahin, M., Benke, T. A., & Downs, J. A. (2022) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-022-02240-w · Cited by 20 · see citing works
The Rare Diseases Clinical Research Network: a model for clinical trial readiness
Lumsden, J. M., & Urv, T. K. (2023) · Therapeutic Advances in Rare Disease · doi:10.1177/26330040231219272 · Cited by 21 · see citing works
Development of trofinetide for the treatment of Rett syndrome: from bench to bedside
Kennedy, M., Glass, L., Glaze, D. G., Kaminsky, S., Percy, A. K., Neul, J. L., Jones, N. E., Tropea, D., Horrigan, J. P., Nues, P., et al. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1341746 · Cited by 19 · see citing works
Self-citation
Disease-Targeted Treatment Translation in Fragile X Syndrome as a Model for Neurodevelopmental Disorders
Berry‐Kravis, E. (2022) · Journal of Child Neurology · doi:10.1177/08830738221089740 · Cited by 18 · see citing works
Self-citation
Recommendations for the management of diarrhea with trofinetide use in Rett syndrome
Marsh, E. D., Beisang, A., Buie, T. M., Benke, T. A., Gaucher, B., & Motil, K. J. (2023) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2023.2217328 · Cited by 17 · see citing works
Intellectual and Developmental Disabilities Research Centers: A Multidisciplinary Approach to Understand the Pathogenesis of Methyl-CpG Binding Protein 2-related Disorders
Fagiolini, M., Patrizi, A., LeBlanc, J. J., Jin, L., Maezawa, I., Sinnett, S. E., Gray, S. J., Molholm, S., Foxe, J. J., Johnston, M. V., et al. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.04.037 · Cited by 17 · see citing works
Gastrointestinal Health Questionnaire for Rett Syndrome
Motil, K. J., Khan, N., Coon, J. L., Barrish, J. O., Suter, B., Pehli̇van, D., Schultz, R., & Glaze, D. G. (2020) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000002951 · Cited by 16 · see citing works
Cyclic Glycine-Proline (cGP) Normalises Insulin-Like Growth Factor-1 (IGF-1) Function: Clinical Significance in the Ageing Brain and in Age-Related Neurological Conditions
Guan, J., Li, F., Kang, D., Anderson, T., Pitcher, T. L., Dalrymple‐Alford, J. C., Shorten, P. R., & Singh‐Mallah, G. (2023) · Molecules · doi:10.3390/molecules28031021 · Cited by 16 · see citing works
Psychometric perspectives on developmental outcome and endpoint selection in treatment trials for genetic conditions associated with neurodevelopmental disorder
Farmer, C., Kaat, A. J., Berry‐Kravis, E., & Thurm, A. E. (2022) · International review of research in developmental disabilities · doi:10.1016/bs.irrdd.2022.05.001 · Cited by 13 · see citing works
Self-citation
Trofinetide in Rett syndrome: A brief review of safety and efficacy
Singh, A., Balasundaram, M. K., & Gupta, D. (2023) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2023.01060 · Cited by 13 · see citing works
Psychometric Assessment of the Rett Syndrome Caregiver Assessment of Symptom Severity (RCASS)
Raspa, M., Gwaltney, A. Y., Bann, C., von Hehn, J., Benke, T. A., Marsh, E. D., Peters, S. U., Ananth, A., Percy, A. K., & Neul, J. L. (2024) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-024-06238-0 · Cited by 12 · see citing works
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
Aishworiya, R., Valica, T., Hagerman, R. J., & Restrepo, B. (2024) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.24022006 · Cited by 15 · see citing works
Self-citation
Profile of Trofinetide in the Treatment of Rett Syndrome: Design, Development and Potential Place in Therapy
Camillo, L., Pozzi, M., Bernardo, P., Pisano, S., & Nobile, M. (2024) · Drug Design Development and Therapy · doi:10.2147/dddt.s383133 · Cited by 12 · see citing works
Organic features of autonomic dysregulation in paediatric brain injury – Clinical and research implications for the management of patients with Rett syndrome
Singh, J., Lanzarini, E., & Santosh, P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.08.012 · Cited by 12 · see citing works
Electrophysiological Biomarkers in Genetic Epilepsies
Armstrong, C., & Marsh, E. D. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01132-4 · Cited by 12 · see citing works
Associations between genotype, phenotype and behaviours measured by the Rett syndrome behaviour questionnaire in Rett syndrome
Downs, J. A., Wong, K., & Leonard, H. (2024) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-024-09575-4 · Cited by 11 · see citing works
International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA
Downs, J., Pichard, D. C., Kaufmann, W. E., Horrigan, J. P., Raspa, M., Townend, G., Marsh, E. D., Leonard, H., Motil, K., Dietz, A. C., et al. (2024) · Trials · doi:10.1186/s13063-024-08678-6 · Cited by 10 · see citing works
Self-citation
Cyclic glycine-proline administration normalizes high-fat diet-induced synaptophysin expression in obese rats
Li, F., Liu, K., Wang, A., Harris, P. W. R., Vickers, M. H., & Guan, J. (2019) · Neuropeptides · doi:10.1016/j.npep.2019.05.006 · Cited by 11 · see citing works
Fragile X Syndrome: Lessons Learned and What New Treatment Avenues Are on the Horizon
Hagerman, R. J., & Hagerman, P. J. (2021) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-052120-090147 · Cited by 12 · see citing works
Self-citation
Targeted Treatments for Fragile X Syndrome
Johnson, D., Clark, C. J., & Hagerman, R. J. (2023) · Advances in neurobiology · doi:10.1007/978-3-031-21054-9_10 · Cited by 10 · see citing works
Self-citation
Exploring Sources, Biological Functions, and Potential Applications of the Ubiquitous Marine Cyclic Dipeptide: A Concise Review of Cyclic Glycine-Proline
Hu, L., Lin, J., Qin, F., Xu, L., & Luo, L. (2024) · Marine Drugs · doi:10.3390/md22060271 · Cited by 10 · see citing works
Insulin-Like Growth Factor 1 Has the Potential to Be Used as a Diagnostic Tool and Treatment Target for Autism Spectrum Disorders
Shen, J., Liu, L., Yang, Y., Zhou, M., Xu, S., Zhang, W., & Zhang, C. (2024) · Cureus · doi:10.7759/cureus.65393 · Cited by 10 · see citing works
Characterization of the Pharmacokinetics and Mass Balance of a Single Oral Dose of Trofinetide in Healthy Male Subjects
Darwish, M., Núñez, R., Youakim, J. M., & Robertson, P. (2023) · Clinical Drug Investigation · doi:10.1007/s40261-023-01322-2 · Cited by 9 · see citing works
Inhibitory Synaptic Influences on Developmental Motor Disorders
Fogarty, M. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086962 · Cited by 9 · see citing works
Safety and efficacy of trofinetide in Rett syndrome: a systematic review and meta-analysis of randomized controlled trials
Abbas, A., Fayoud, A. M., Moawad, M. H. E. D., Hamad, A. A., Hamouda, H., & Fouad, E. A. (2024) · BMC Pediatrics · doi:10.1186/s12887-024-04526-3 · Cited by 10 · see citing works
Drug Treatments for Neurodevelopmental Disorders: Targeting Signaling Pathways and Homeostasis
Kaufmann, W. E., Luu, S., & Budimirovic, D. B. (2024) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-024-01394-3 · Cited by 8 · see citing works
AI-enabled drug prediction and gene network analysis reveal therapeutic use of vorinostat for Rett Syndrome in preclinical models
Novak, R., Lin, T., Kaushal, S., Sperry, M. M., Vigneault, F., Gardner, E., Loomba, S., Shcherbina, K., Keshari, V., Dinis, A., et al. (2025) · Communications Medicine · doi:10.1038/s43856-025-00975-8 · Cited by 8 · see citing works
Exposure–Response Efficacy Modeling to Support Trofinetide Dosing in Individuals with Rett Syndrome
Darwish, M., Passarell, J. A., Youakim, J. M., Bradley, H., & Bishop, K. M. (2024) · Advances in Therapy · doi:10.1007/s12325-024-02796-y · Cited by 8 · see citing works
High Throughput Small Molecule Screen for Reactivation of FMR1 in Fragile X Syndrome Human Neural Cells
Hunt, J. F. V., Li, M., Risgaard, R. D., Ananiev, G. E., Wildman, S. A., Zhang, F., Bugni, T. S., Zhao, X., & Bhattacharyya, A. (2021) · Cells · doi:10.3390/cells11010069 · Cited by 8 · see citing works
Evaluation Tools Developed for Rett Syndrome
Lotan, M., Downs, J. A., Stahlhut, M., & Romano, A. (2023) · Diagnostics · doi:10.3390/diagnostics13101708 · Cited by 7 · see citing works
Research Gaps in Fragile X Syndrome: An Updated Literature Review to Inform Clinical and Public Health Practice
Raspa, M., Wheeler, A., Okoniewski, K. C., Edwards, A., & Scott, S. (2022) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0000000000001134 · Cited by 6 · see citing works
Managing Gastrointestinal Symptoms Resulting from Treatment with Trofinetide for Rett Syndrome: Caregiver and Nurse Perspectives
Moore, R., Poulsen, J., Reardon, L., Samples-Morris, C., Simmons, H., Ramsey, K. M., Whatley, M. L., & Lane, J. B. (2024) · Advances in Therapy · doi:10.1007/s12325-024-02782-4 · Cited by 6 · see citing works
The novel potent GSK3 inhibitor AF3581 reverts fragile X syndrome phenotype
Porceddu, P. F., Ciampoli, M., Romeo, E., Garrone, B., Durando, L., Milanese, C., Giorgio, F. P. D., & Reggiani, A. M. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab251 · Cited by 6 · see citing works
Molecular Signatures of Response to Mecasermin in Children With Rett Syndrome
Shovlin, S., Delepine, C., Swanson, L. C., Bach, S., Şahin, M., Sur, M., Kaufmann, W. E., & Tropea, D. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.868008 · Cited by 6 · see citing works
Pharmacological management of fragile X syndrome: a systematic review and narrative summary of the current evidence
Watkins, L. V., Moon, S., Burrows, L., Tromans, S. J., Barwell, J., & Shankar, R. (2024) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2024.2323605 · Cited by 5 · see citing works
Physiologically-Based Pharmacokinetic Modeling of Trofinetide in Moderate Renal Impairment for Phase 1 Clinical Study Dose Selection with Model Validation
Darwish, M., Marbury, T. C., Núñez, R., Youakim, J. M., An, D., Darling, I. M., Lukáčová, V., & Bishop, K. M. (2024) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-024-00924-1 · Cited by 5 · see citing works
A meta-analysis of the efficacy and safety of trofinetide in patients with rett syndrome
Zeid, M. A., Elrosasy, A., Mohamed, R. G., Ghazou, A., Goufa, E., Hassan, N., & Abuzaid, Y. (2024) · Neurological Sciences · doi:10.1007/s10072-024-07584-8 · Cited by 5 · see citing works
Neuroinflammation links COVID-19 and fragile X syndrome: Role of MMP-9, IGF-1, IL-10, metformin, statins and curcuminPreprint
Altable, M. (2021) · doi:10.32388/ko4c77 · Cited by 3 · see citing works
Neuroinflammation and autism: what have we learned so far?
Aytulun, A., & Ünal, D. (2024) · International Journal of Developmental Disabilities · doi:10.1080/20473869.2024.2366722 · Cited by 4 · see citing works
Neuroinflammation links COVID-19 and fragile X syndrome: Role of MMP-9, IGF-1, IL-10, metformin, statins and curcuminPreprint
Altable, M., & de la Serna, J. M. (2021) · doi:10.32388/ko4c77.2 · Cited by 3 · see citing works
Discovery of hybrid Glypromate conjugates with neuroprotective activity against paraquat-induced toxicity
Silva-Reis, S. C., Costa, V. M., da Silva, D. C., Pereira, D. M., Correia, X. C., Xerardo Garcia-mera, B., Rodríguez-Borges, J. E., & Sampaio‐Dias, I. E. (2024) · RSC Medicinal Chemistry · doi:10.1039/d4md00584h · Cited by 3 · see citing works
Behavioural difficulties in fragile X syndrome: current pharmacological options and potential future developments
Stanfield, A. C., & McKechanie, A. G. (2025) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2025.2510408 · Cited by 3 · see citing works
Molecular mechanisms for targeted treatments in fragile X syndrome
Miranda, I., & Hagerman, R. J. (2023) · Rare Disease and Orphan Drugs Journal · doi:10.20517/rdodj.2023.21 · Cited by 3 · see citing works
Self-citation
Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials
Mohammed, H. E., Bady, Z. A. M., Haseeb, M. E., Aboeldahab, H. A., Sharaf‐Eldin, W. E., & Zaki, M. S. (2024) · BMC Medicine · doi:10.1186/s12916-024-03506-9 · Cited by 3 · see citing works
Turning the tide on targeted treatments for neurodevelopmental disorders
Hagerman, R. J., & Tuchman, R. F. (2019) · Neurology · doi:10.1212/wnl.0000000000007301 · Cited by 3 · see citing works
Self-citation
Association of Thyroid Hormone and Insulin‐Like Growth Factor‐1 Levels With Autism Spectrum Disorders: A Systematic Review and Meta‐Analysis
Long, J., Liao, X., Han, K., Niu, M., Chen, J., Wang, X., Liu, J., Zhang, Y., & Zhang, H. (2025) · Autism Research · doi:10.1002/aur.70052 · Cited by 2 · see citing works
Symptom Onset in Classic Rett Syndrome: Analysis of Initial Clinical Severity Scale Entries
Percy, A. K., Neul, J. L., Ananth, A., Benke, T. A., & Marsh, E. D. (2025) · Annals of the Child Neurology Society · doi:10.1002/cns3.70017 · Cited by 2 · see citing works
Population Pharmacokinetic Modeling to Support Trofinetide Dosing for the Treatment of Rett Syndrome
Darwish, M., Passarell, J. A., Maxwell, K., Youakim, J. M., Bradley, H., & Bishop, K. M. (2024) · Advances in Therapy · doi:10.1007/s12325-024-03056-9 · Cited by 2 · see citing works
Fragile X Syndrome: Supportive Treatment, Unmet Needs, and Paths to Novel Interventions and Disease-Targeted Therapies
Berry‐Kravis, E. (2022) · American Journal on Intellectual and Developmental Disabilities · doi:10.1352/1944-7558-127.2.90 · Cited by 2 · see citing works
Self-citation
Points to consider when initiating clinical investigations in autistic paediatric populations-A White Paper.
Ham, L. M., Staunton, H., Schulz, J. M., Tillmann, J., Volz, D., Murtagh, L., Chatham, C., O’Connor, E. C., Chamberlain, S., Schoenenberger, P., et al. (2024) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2024.05.011 · Cited by 3 · see citing works
Trofinetide approved for children and adults with Rett syndrome (RTT): A therapeutics bulletin of the American College of Medical Genetics and Genomics (ACMG)
Selvam, P., Beltran, C. F. M., Sen, K., & Morales, A. (2024) · Genetics in Medicine Open · doi:10.1016/j.gimo.2024.101856 · Cited by 1 · see citing works
Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways
Verma, J., Singh, R. K., Paul, S., Gupta, S., Gupta, A. K., Sharma, A. K., Kumar, M., Mehan, S., Samant, R., & Tongra, M. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01866-0 · Cited by 1 · see citing works
Direct Benefit, Equipoise, and Research on the Non-consenting
Napier, S. R. (2023) · Philosophy and medicine · doi:10.1007/978-3-031-12692-5_11 · Cited by 1 · see citing works
Phenotypic Trade-Offs: Deciphering the Impact of Neurodiversity on Drug Development in Fragile X Syndrome
Bui, T. A., Shatto, J., Cuppens, T., Droit, A., & Bolduc, F. V. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.730987 · Cited by 1 · see citing works
Fragile X syndrome - insight into what we know and prospects
Strzoda, A. J., Kamińska, M., Strzoda, A., Strzoda, A., Sowiński, W. J., Zdybel, M., Agata, J. U. D. A., & Rojek, K. (2023) · Journal of Education Health and Sport · doi:10.12775/jehs.2023.19.01.006
The Possible Role of Postnatal Biphasic Dysregulation of IGF-1 Tone in the Etiology of Idiopathic Autism Spectrum Disorder
Visegrády, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104483 · Cited by 1 · see citing works
Treatment of Neurodevelopmental Disorders
van Karnebeek, C., Berry‐Kravis, E., & Gropman, A. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-10944-7.00079-2
Self-citation
Breathing Dysfunction as a Meaningful and Measurable Aspect of Health in Rett Syndrome: A Caregiver’s Perspective
Wright, R., Li, J., Blankenship, J. M., Richards, J. C., Coenraads, M., von Hehn, J., Clay, I., Lyden, K. A., & Leonard-Corzo, K. S. (2025) · Digital Biomarkers · doi:10.1159/000548358
Additional file 1 of Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials
Mohammed, H. E., Bady, Z. A. M., Haseeb, M. E., Aboeldahab, H. A., Sharaf-Eldin, W. E., & Zaki, M. S. (2024) · Figshare · doi:10.6084/m9.figshare.26322596

A Randomized Double-Blind, Placebo-Controlled Trial of Minocycline in Children and Adolescents with Fragile X Syndrome
Leigh, M. J. S., Nguyen, D. V., Mu, Y., Winarni, T. I., Schneider, A., Chechi, T., Polussa, J., Doucet, P., Tassone, F., Rivera, S. M., et al. (2013) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/dbp.0b013e318287cd17 · Cited by 298 · see citing works
Self-citation
Double‐blind, placebo‐controlled crossover study of folinic acid (Leucovorin®) for the treatment of fragile X syndrome
Strom, C. M., Brusca, R. M., & Pizzi, W. J. (1992) · American Journal of Medical Genetics · doi:10.1002/ajmg.1320440529 · Cited by 24 · see citing works
Effectiveness and Safety of Donepezil in Boys With Fragile X Syndrome
Sahu, J. K., Gulati, S., Sapra, S., Arya, R., Chauhan, S., Chowdhury, M. R., Gupta, N., Kabra, M., Gupta, Y. K., Dwivedi, S. N., et al. (2012) · Journal of Child Neurology · doi:10.1177/0883073812449381 · Cited by 34 · see citing works
Folic acid for fragile X syndrome
Rueda, J.-R., Ballesteros, J., Guillén, V., Tejada, M., & Solà, I. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008476.pub2 · Cited by 15 · see citing works
Arbaclofen in fragile X syndrome: results of phase 3 trials
Berry-Kravis, E., Hagerman, R., Visootsak, J., Budimirovic, D., Kaufmann, W. E., Cherubini, M., Zarevics, P., Walton-Bowen, K., Wang, P., Bear, M. F., et al. (2017) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-016-9181-6 · Cited by 183 · see citing works
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Authors: Berry-Kravis, E., Horrigan, J. P., Tartaglia, N., Hagerman, R., Kolevzon, A., Erickson, C. A., Hatti, S., Snape, M., Yaroshinsky, A., Stoms, G., Sanders, K., Frazier, J., Challman, T., Innis, J., King, B., Cubells, J., Visootsak, J., Skinner, S., Treadwell-Deering, D., Vinson, S. S., Needelman, H., Glass, L., & Jones, N. E.
Affiliations: Duke University (US)
Children's Hospital Colorado (US)
University of California, Davis (US)
Mount Sinai Hospital (US)
Cincinnati Children's Hospital Medical Center (US)
Suburban Research Associates (US)
AMO Pharma (United Kingdom) (GB)
ORCID: Horrigan, Joseph P.
Tartaglia, Nicole
Hagerman, Randi
Kolevzon, Alexander
Erickson, Craig A.
Snape, Mike
Yaroshinsky, Alex
Stoms, George
Sanders, Kevin
Frazier, Jean
Challman, Thomas
Innis, Jeffrey
Cubells, Joseph
Visootsak, Jeannie
Skinner, Steven
Needelman, Howard
Glass, Larry
Jones, Nancy E.
Venue: Pediatric Neurology
Publisher: Elsevier BV
Published: 2020-09
Volume: 110
Pages: 30-41
ISSN: 0887-8994 (ISSN-L)
DOI: 10.1016/j.pediatrneurol.2020.04.019
OpenAlex: W2734032654
Cited by: 102
References: 50
Citations by year: 2026: 3 · 2025: 6 · 2024: 25 · 2023: 18 · 2022: 12 · 2021: 13 · 2020: 15 · 2019: 7 · 2018: 3
FWCI: 8.50
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Pediatric Neurology (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: Neuren Pharmaceuticals, Ltd
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords: trofinetide, fragile X syndrome, FMRP, safety and tolerability, efficacy, symptom domains, dose comparison
MeSH terms: Adolescent, Adult, Child, Double-Blind Method, Fragile X Syndrome, Glutamates, Humans, Male, Outcome Assessment, Health Care, Young Adult

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A double-blind, randomized, placebo-controlled clinical study of trofinetide in the treatment of fragile X syndrome

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