在发育突触症中表征发育和行为特征,以告知临床试验终点
Latha Valluripalli Soorya1, Camille W Brune1, Cristan A Farmer1
1Latha Valluripalli Soorya, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Camille W. Brune, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Cristan A. Farmer, Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health; Edith V. Ocampo, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Natalie I. Berger, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Deborah A. Pearson, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston; Robyn M. Busch, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and Department of Neurology and Epilepsy Center, Cleveland Clinic; Patricia Klaas, Center for General Neurology, Cleveland Clinic; Paige Siper, Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai; Kristn Currans, Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center; Amanda C. Gulsrud, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles; Jennifer M. Phillips, Department of Psychiatry and Behavioral Sciences, Stanford University, Rajna Filip-Dhima, Department of Neurology, Boston Children's Hospital, Harvard University; Sarah E. O'Kelley, Department of Psychology and Pediatrics, University of Alabama at Birmingham; Thomas W. Frazier, Department of Psychology, John Carroll University, Research Faculty, Departments of Pediatrics and Psychiatry at SUNY Upstate Medical University; Tess Levy, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai; Allison L. Wainer, Department of Psychiatry & Behavioral Sciences, Rush University Medical Center; Joseph D. Buxbaum, Seaver Autism Center, Icahn School of Medicine at Mount Sinai; Craig M. Powell, Civitan International Research Center, University of Alabama at Birmingham; Jonathan A. Bernstein, Stanford University School of Medicine; Simon K. Warfield, Harvard University Medical School, and Department of Radiology, Boston Children's Hospital; Darcy A. Krueger, Cincinnati Children's Hospital Medical Center; E. Martina Bebin, University of Alabama at Birmingham; Hope Northrup, Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) and Children's Memorial Hermann Hospital, Shafali S. Jeste, Keck School of Medicine, University of Southern California, and Children's Hospital Los Angeles; Alexander Kolevzon, Icahn School of Medicine at Mount Sinai; Elizabeth Berry-Kravis, Rush University Medical Center; Mustafa Sahin, Department of Neurology, Boston Children's Hospital, Harvard Medical School; Siddharth Srivastava, Boston Children's Hospital and Assistant Professor of Neurology, Harvard Medical School; Audrey Thurm, Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, National Institutes of Health.
标准的认知和行为评估通常不适合患有罕见神经遗传疾病的儿童,如菲兰-麦克德米德综合征,结核硬化综合征和PTEN哈马托马瘤综合征,因为智力障碍严重,影响临床试验准备.
科学领域:
- 神经遗传学
- 发展神经科学
- 临床试验设计
背景情况:
- 发展性突触症联盟研究罕见的神经遗传综合征.
- 临床试验准备是一个关键目标,需要验证的结果措施.
- 菲兰- 麦克德米德综合征 (PMS),结核性硬化综合征 (TSC) 和PTEN哈马托马瘤综合征 (PHTS) 是目标疾病.
研究的目的:
- 评估当前认知和行为评估的范围和局限性.
- 在特定神经发育条件下测量临床概念准备的挑战.
主要方法:
- 对2至21岁的PMS (N=98),TSC (N=98) 和PHTS (N=69) 的自然史研究.
- 对认知和行为测量策略的评估.
- 分析智力障碍的严重程度及其对评估有效性的影响.
主要成果:
- 智力障碍的严重程度各不相同:在PMS中严重到严重,在TSC中轻度到中度,在PHTS中边缘/缺席.
- 智力障碍的严重程度使许多标准评估无效,
- 目前对这些群体的测量策略中发现的局限性.
结论:
- 对于PMS,TSC和PHTS严重智力障碍的儿童来说,传统的认知和行为措施往往是不够的.
- 这些发现突显了罕见神经发育障碍临床试验规划的关键差距.
- 修订评估策略对于推进临床研究和试验准备至关重要.
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