دورية أكاديمية
A randomized controlled trial of levodopa in patients with Angelman syndrome.
| العنوان: | A randomized controlled trial of levodopa in patients with Angelman syndrome. |
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| المؤلفون: | Tan WH; Division of Genetics and Genomics, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts., Bird LM; Genetics / Dysmorphology, Rady Children's Hospital San Diego; Department of Pediatrics, University of California, San Diego, California., Sadhwani A; Department of Psychiatry, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts., Barbieri-Welge RL; Developmental Services, Rady Children's Hospital San Diego, San Diego, California., Skinner SA; Greenwood Genetic Center, Greenwood, South Carolina., Horowitz LT; Greenwood Genetic Center, Greenwood, South Carolina., Bacino CA; Genetics Service, Texas Children's Hospital; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas., Noll LM; Psychology Service, Texas Children's Hospital; Baylor College of Medicine, Houston, Texas., Fu C; Division of Pediatric Neurology, Vanderbilt University School of Medicine, Nashville, Tennessee., Hundley RJ; Division of Developmental Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee., Wink LK; Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Erickson CA; Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Barnes GN; Division of Pediatric Neurology, Vanderbilt University School of Medicine, Nashville, Tennessee., Slavotinek A; Department of Pediatrics, University of California, San Francisco, California., Jeremy R; Department of Pediatrics, University of California, San Francisco, California., Rotenberg A; Department of Neurology, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts., Kothare SV; Department of Neurology, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts., Olson HE; Department of Neurology, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts., Poduri A; Department of Neurology, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts., Nespeca MP; Neurology, Rady Children's Hospital San Diego; University of California, San Diego, California., Chu HC; Division of Genetics and Genomics, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts., Willen JM; Division of Genetics and Genomics, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts., Haas KF; Department of Neurology, Vanderbilt University School of Medicine, Nashville, Tennessee., Weeber EJ; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida., Rufo PA; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, Massachusetts. |
| المصدر: | American journal of medical genetics. Part A [Am J Med Genet A] 2018 May; Vol. 176 (5), pp. 1099-1107. Date of Electronic Publication: 2017 Sep 25. |
| نوع المنشور: | Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Hoboken, N.J. : Wiley-Blackwell Original Publication: Hoboken, N.J. : Wiley-Liss, c2003- |
| مواضيع طبية MeSH: | Angelman Syndrome/*drug therapy , Levodopa/*therapeutic use, Angelman Syndrome/diagnosis ; Angelman Syndrome/physiopathology ; Angelman Syndrome/psychology ; Animals ; Biomarkers ; Calcium/metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Disease Models, Animal ; Humans ; Levodopa/administration & dosage ; Long-Term Potentiation ; Mice ; Neuropsychological Tests ; Treatment Outcome |
| مستخلص: | Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium/calmodulin-dependent kinase II. Further studies demonstrated that AS mice treated with levodopa performed better on rotarod testing than untreated AS mice. We conducted a multi-center double-blind randomized placebo-controlled 1-year trial of levodopa / carbidopa with either 10 or 15 mg/kg/day of levodopa in children with AS. The outcome of this intervention was assessed using either the Bayley Scales of Infant Development or the Mullen Scales of Early Learning, as well as the Vineland Adaptive Behavior Scales, and the Aberrant Behavior Checklist. Of the 78 participants enrolled, 67 participants received study medication (33 on levodopa, 34 on placebo), and 55 participants (29 on levodopa, 26 on placebo) completed the 1-year study. There were no clinically or statistically significant changes in any of the outcome measures over a 1-year period comparing the levodopa and placebo groups. The number of adverse events reported, including the more serious adverse events, was similar in both groups, but none were related to treatment with levodopa. Our data demonstrate that levodopa is well-tolerated by children with AS. However, in the doses used in this study, it failed to improve their neurodevelopment or behavioral outcome. (© 2017 Wiley Periodicals, Inc.) |
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| معلومات مُعتمدة: | U54 HD061222 United States HD NICHD NIH HHS; UL1 TR000170 United States TR NCATS NIH HHS; R01 FD003523 United States FD FDA HHS; UL1 TR001425 United States TR NCATS NIH HHS; U54 HD090255 United States HD NICHD NIH HHS |
| فهرسة مساهمة: | Keywords: UBE3A; calcium-calmodulin-dependent protein kinase type 2; clinical trial; developmental disabilities; inborn genetic diseases; rare disease |
| المشرفين على المادة: | 0 (Biomarkers) 46627O600J (Levodopa) EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) SY7Q814VUP (Calcium) |
| تواريخ الأحداث: | Date Created: 20170926 Date Completed: 20190520 Latest Revision: 20210930 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5867193 |
| DOI: | 10.1002/ajmg.a.38457 |
| PMID: | 28944563 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1552-4833 |
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| DOI: | 10.1002/ajmg.a.38457 |