脆性X综合征药物治疗进展

梅练妮; 胡纯纯; 徐琼

doi:10.11852/zgetbjzz2022-0958

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中国儿童保健杂志 ›› 2023, Vol. 31 ›› Issue (2) : 180-184. DOI: 10.11852/zgetbjzz2022-0958

综述

脆性X综合征药物治疗进展

梅练妮, 胡纯纯, 徐琼

作者信息 +

Progress in drug therapy for fragile X syndrome

MEI Lian-ni, HU Chun-chun, XU Qiong

Author information +

文章历史 +

摘要

脆性X综合征(FXS)是一种神经发育障碍性疾病,是遗传性智力障碍最常见的病因,也是孤独症谱系障碍最主要的单基因缺陷。FXS主要表现为认知障碍、特殊面容、行为问题及其他多系统异常。本文综述针对FXS异常神经生物机制进行调节的药物,以期提供相应药物治疗FXS有效性与安全性的汇总数据。

Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is the most common inherited cause of intellectual disability(ID) and the most prevalent monogenic cause of autism spectrum disorder (ASD). FXS is characterized by cognitive deficits, special facial features, behavioral problems and other multi-system abnormalities. This review combs the drugs that regulate abnormal neurobiology of FXS, in order to provide integrative data of the efficacy and safety of drugs therapy in FXS treatment.

导出引用

梅练妮, 胡纯纯, 徐琼. 脆性X综合征药物治疗进展[J]. 中国儿童保健杂志. 2023, 31(2): 180-184 https://doi.org/10.11852/zgetbjzz2022-0958

MEI Lian-ni, HU Chun-chun, XU Qiong. Progress in drug therapy for fragile X syndrome[J]. Chinese Journal of Child Health Care. 2023, 31(2): 180-184 https://doi.org/10.11852/zgetbjzz2022-0958

中图分类号： R741

参考文献

[1] Hagerman RJ, Berry-Kravis E, Hazlett HC, et al. Fragile X syndrome[J]. Nat Rev Dis Primers, 2017,3(1):17065.
[2] Mila M, Alvarez-Mora MI, Madrigal I, et al. Fragile X syndrome:An overview and update of the FMR1 gene[J]. Clin Genet, 2018,93(2):197-205.
[3] Zafarullah M, Tassone F. Molecular biomarkers in fragile X syndrome[J]. Brain Sci, 2019,9(5):96.
[4] Raspa M, Wheeler AC, Riley C. Public health literature review of fragile X syndrome[J]. Pediatrics, 2017,139(Suppl 3):153-171.
[5] Gantois I, Khoutorsky A, Popic J, et al. Metformin ameliorates core deficits in a mouse model of fragile X syndrome[J]. Nat Med, 2017,23(6):674-677.
[6] Monyak RE, Emerson D, Schoenfeld BP, et al. Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model[J]. Mol Psychiatry, 2017,22(8):1140-1148.
[7] Dy A, Tassone F, Eldeeb M, et al. Metformin as targeted treatment in fragile X syndrome[J]. Clin Genet, 2018,93(2):216-222.
[8] Protic D, Aydin EY, Tassone F, et al. Cognitive and behavioral improvement in adults with fragile X syndrome treated with metformin-two cases[J]. Mol Genet Genomic Med, 2019,7(7):e745.
[9] Biag H, Potter LA, Wilkins V, et al. Metformin treatment in young children with fragile X syndrome[J]. Mol Genet Genomic Med, 2019,7(11):e956.
[10] Mélodie P, Angélina L, Luc G, et al. The safety and efficacy of metformin in fragile X syndrome:An open-label study[J].Prog Neuro-Psychoph,2021,110:307.
[11] Muscas M, Louros SR, Osterweil EK. Lovastatin, not Simvastatin, Corrects Core Phenotypes in the Fragile X Mouse Model[J]. eNeuro, 2019,6(3):19-97.
[12] Asiminas A, Jackson AD, Louros SR, et al. Sustained correction of associative learning deficits after brief, early treatment in a rat model of Fragile X Syndrome[J]. Sci Transl Med, 2019,11(494):o498.
[13] Çaku A, Pellerin D, Bouvier P, et al. Effect of lovastatin on behavior in children and adults with fragile X syndrome:An open-label study[J]. Am J Med Genet A, 2014,164A(11):2834-2842.
[14] Thurman AJ, Potter LA, Kim K, et al. Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome[J]. J Neurodev Disord, 2020,12(1):12.
[15] Pellerin D, Çaku A, Fradet M, et al. Lovastatin corrects ERK pathway hyperactivation in fragile X syndrome:Potential of platelet′s signaling cascades as new outcome measures in clinical trials[J]. Biomarkers, 2016,21(6):497-508.
[16] Yau SY, Bettio L, Vetrici M, et al. Chronic minocycline treatment improves hippocampal neuronal structure, NMDA receptor function, and memory processing in Fmr1 knockout mice[J]. Neurobiol Dis, 2018,113:11-22.
[17] Yau SY, Chiu C, Vetrici M, et al. Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice[J]. Behav Brain Res, 2016,312:77-83.
[18] Toledo MA, Wen TH, Binder DK, et al. Reversal of ultrasonic vocalization deficits in a mouse model of Fragile X Syndrome with minocycline treatment or genetic reduction of MMP-9[J]. Behav Brain Res, 2019,372:112068.
[19] Leigh MJ, Nguyen DV, MuY, et al. A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome[J]. J Dev Behav Pediatr, 2013,34(3):147-155.
[20] Magdalena D, Dalyir IP, Aleksandra J, et al. High MMP-9 activity levels in fragile X syndrome are lowered by minocycline[J]. Am J Med Genet A, 2013,161A(8):897-903.
[21] Qin M, Zeidler Z, Moulton K, et al. Endocannabinoid-mediated improvement on a test of aversive memory in a mouse model of fragile X syndrome[J]. Behav Brain Res, 2015,291:164-171.
[22] Zieba J, Sinclair D, Sebree T, et al. Cannabidiol (CBD) reduces anxiety-related behavior in mice via an FMRP-independent mechanism[J]. Pharmacol Biochem Behav, 2019,181:93-100.
[23] Tartaglia N, Bonn-Miller M, Hagerman R. Treatment of Fragile X syndrome with cannabidiol:A case series study and brief review of the literature[J]. Cannabis Cannabinoid Res, 2019,4(1):3-9.
[24] Heussler H, Cohen J, Silove N, et al. A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome[J]. J Neurodev Disord, 2019,11(1):16.
[25] Hanson AC, Hagerman RJ. Serotonin dysregulation in Fragile X Syndrome:Implications for treatment[J]. Intractable Rare Dis Res, 2014,3(4):110-117.
[26] Indah WT, Chonchaiya W, Adams E, et al. Sertraline may improve language developmental trajectory in young children with fragile x syndrome:A retrospective chart review[J]. Autism Res Treat, 2012,2012:104317.
[27] Greiss HL, Fitzpatrick SE, Nguyen DV, et al. A randomized, double-blind, placebo-controlled trial of low-dose sertraline in young children with fragile X syndrome[J]. J Dev Behav Pediatr, 2016,37(8):619-628.
[28] Pop AS, Levenga J, de Esch CE, et al. Rescue of dendritic spine phenotype in Fmr1 KO mice with the mGluR5 antagonist AFQ056/Mavoglurant[J]. Psychopharmacology(Berl), 2014,231(6):1227-1235.
[29] Zerbi V, Markicevic M, Gasparini F, et al. Inhibiting mGluR5 activity by AFQ056/Mavoglurant rescues circuit-specific functional connectivity in Fmr1 knockout mice[J]. Neuroimage, 2019,191:392-402.
[30] Berry-Kravis E, Des Portes V, Hagerman R, et al. Mavoglurant in fragile X syndrome:Results of two randomized,double-blind,placebo-controlled trials[J]. Sci Transl Med, 2016,8(321):321r-325r.
[31] Hessl D, Harvey D, Sansone S, et al. Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome[J]. PLoS One, 2019,14(1):e209984.
[32] Youssef EA, Berry-Kravis E, Czech C, et al. Effect of the mGluR5-NAM Basimglurant on behavior in adolescents and adults with fragile X syndrome in a randomized, double-blind, placebo-controlled trial:FragXis phase 2 results[J]. Neuropsychopharmacology, 2018,43(3):503-512.
[33] Henderson C, Wijetunge L, Kinoshita MN, et al. Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen[J]. Sci Transl Med, 2012,4(152):128r-152r.
[34] Berry-Kravis E, Hagerman R, Visootsak J, et al. Arbaclofen in fragile X syndrome:Results of phase 3 trials[J]. J Neurodev Disord, 2017,9:3.
[35] Schaefer TL, Davenport MH, Grainger LM, et al. Acamprosate in a mouse model of fragile X syndrome:Modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety[J]. J Neurodev Disord, 2017,9:6.
[36] Hutson RL, Thompson RL, Bantel AP, et al. Acamprosate rescues neuronal defects in the Drosophila model of Fragile X Syndrome[J]. Life Sci, 2018,195:65-70.
[37] Erickson CA, Wink LK, Ray B, et al. Impact of acamprosate on behavior and brain-derived neurotrophic factor:An open-label study in youth with fragile X syndrome[J]. Psychopharmacology (Berl), 2013,228(1):75-84.
[38] Ligsay A, Van Dijck A, Nguyen DV, et al. A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome[J]. J Neurodev Disord, 2017,9(1):26.