Body Composition and Energy Utilization in Spinal Muscular Atrophy

脊髓性肌萎缩症的身体成分和能量利用

• 批准号: 8384332
• 负责人: Douglas Michael Sproule
• 金额: $ 4.37万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-17 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8384332
• 关键词: 2 year old; Acceleration; Adult; Advanced Development; Affect; Area; Attention; Biological Markers; Body Composition; Child; Childhood; Clinical; Clinical Management; Clinical Research; Clinical Trials; Data; Development; Diet; Diet and Nutrition; Disease; Disease Progression; Doctor of Medicine; Doctor of Philosophy; Educational Curriculum; Energy Intake; Energy Metabolism; Equilibrium; Fatty acid glycerol esters; Flexor; Food; Funding; Gastrostomy; Genetic; Goals; Human; Image; Indirect Calorimetry; Infant; Inherited; Institutes; Intake; Investigation; Journals; K-Series Research Career Programs; Knee; Label; Laboratories; Lead; Magnetic Resonance Imaging; Malnutrition; Measurement; Measures; Mechanical ventilation; Mechanics; Medical; Mentors; Mentorship; Metabolic; Modeling; Motor Neurons; Muscle; Muscular Atrophy; Myography; Neuromuscular Diseases; New York; Nutritional; Nutritional Study; Obesity; Outcome; Paralysed; Patients; Peer Review; Pharmacotherapy; Phase I Clinical Trials; Positioning Attribute; Quality of life; Recommendation; Research; Research Institute; Research Personnel; Research Project Grants; Rest; Role; Severity of illness; Spinal Cord; Spinal Muscular Atrophy; Techniques; Technology; Thigh structure; Torque; Training; Translational Research; Universities; Wasting Syndrome; Water; Werdnig-Hoffmann Disease; Work; base; biceps brachii muscle; clinical application; clinical care; clinical phenotype; disease natural history; effective therapy; electric impedance; energy balance; evidence base; experience; hamstring; improved; improved functioning; infant death; insight; nutrition; outcome forecast; quadriceps muscle; treatment effect; wasting

DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is a hereditary pediatric neuromuscular disease marked by progressive weakness and muscle atrophy resulting from the loss of spinal cord motor neurons. SMA presents across a clinical spectrum, ranging from extremely weak infants with a historically dismal prognosis (Werdnig-Hoffmann, SMA type 1) to mildly affected, ambulatory children and adults (Kugelberg-Welander, SMA type 3). Despite the absence of an effective therapy, aggressive nutritional management (including gastrostomy placement) along with widespread use of mechanical ventilatory support has greatly altered the "natural history" of the disease in recent years. Survival has been particularl improved among children with spinal muscular atrophy type 1. Unfortunately, although nutrition and body composition are a modifiable factors of potential importance in the optimal clinical management of patients with SMA, there is almost no data or peer- reviewed study available to inform this area of clinical care. We propose to study energy expenditure, caloric intake (and therefore caloric balance), and body composition, using state-of-the-art approaches and technology, among children and adults with SMA. We aim to advance the presently limited understanding of nutrition in spinal muscular atrophy. The development of patient- specific dietary recommendations would be of potential clinical benefit to affected patients, and could meaningfully improve the lives of people with SMA. We will also study muscle imaging approaches such as MRI and dual energy x-ray absorptiometry, and electrical impedance myography, for potential use as biomarkers of disease progression in SMA. The development of biomarkers of disease progression (and treatment effect) is critical in the acceleration of early stage clinical trials. My goal is to build a clinical research effort studying nutrition and body composition in SMA, with the ultimate aim of impacting function and outcome of patients with SMA and other pediatric neuromuscular diseases through improvements in clinical care. To this end, I am working with a growing network of colleagues in body composition and energy expenditure, through the New York Obesity Nutrition Research Center (NYONRC), and nutrition, through the Irving Institute for Clinical and Translational Research and Institute of Human Nutrition at Columbia University. My proposal incorporates a comprehensive mentoring and training curriculum that includes: 1) active mentorship from Dr. Dympna Gallagher, Ph.D., a senior researcher with the NYONRC, and Dr. Darryl De Vivo, M.D., an experienced researcher in pediatric neuromuscular disease; 2) formal educational seminars and journal clubs and laboratory training through the NYONRC; 3) coursework activities through the Institute of Nutrition, 4) complementary clinical and clinical research responsibilities; and 5) completion of the proposed research project leading to successful application for independent funding. PUBLIC HEALTH RELEVANCE: We aim to advance evidence-based nutritional management in spinal muscular atrophy (SMA), an untreatable hereditary pediatric neuromuscular disease marked by the loss of spinal cord motor neurons. We will study the relationship between disease severity, body composition and energy expenditure with the goal of informing clinical management and the potential role of nutritional modulation to affect the natural course of the disease. We will also study muscle imaging and electrical impedance as potential biomarkers of disease progression; the development of such biomarkers is of critical importance in the acceleration of clinical trials in SMA.

描述（由申请人提供）：脊柱肌肉萎缩（SMA）是一种遗传性儿科神经肌肉疾病，其逐渐虚弱和脊髓运动神经元的丧失导致进行性无力和肌肉萎缩。 SMA遍布临床光谱，范围从具有历史上惨淡的预后（Werdnig-Hoffmann，SMA 1型）到受到轻度影响的ABSURATONIC CHILDERS和成人（Kugelberg-Welander，SMA 3型）的婴儿。尽管没有有效的疗法，但侵略性营养管理（包括胃造口术）以及广泛使用机械通气支持的方法已大大改变了近年来该疾病的“自然史”。患有1型脊柱肌肉萎缩症的儿童的生存尤其改善。不幸的是，尽管营养和身体成分是SMA患者最佳临床管理中潜在重要性的可修改因素，但几乎没有可用于告知该临床护理领域的数据或同伴审查的研究。我们建议在患有SMA的儿童和成人中使用最先进的方法和技术研究能量消耗，热量摄入量（以及热量平衡）以及身体组成。我们旨在促进目前对脊柱肌肉萎缩中营养的有限理解。患者特定饮食建议的发展对患者有潜在的临床益处，并有意义地改善了SMA患者的生活。我们还将研究肌肉成像方法，例如MRI和双能X射线吸收仪和电阻止myagraphy，以潜在用作SMA疾病进展的生物标志物。疾病进展（和治疗效应）生物标志物的发展对于早期临床试验的加速至关重要。我的目标是建立一项临床研究工作，研究SMA中的营养和身体成分，以通过改善临床护理的改善来影响SMA和其他儿科神经肌肉疾病患者的最终目的。为此，我通过纽约肥胖营养研究中心（NYONRC）（NYONRC）与不断增长的人体组成和能量消耗网络合作，并通过哥伦比亚大学的临床和转化研究所和人类营养研究所。我的提案结合了一项全面的指导和培训课程，其中包括：1）NyonRC的高级研究员Dympna Gallagher博士的积极指导，以及M.D. Darryl de Vivo博士，是儿科神经肌肉疾病的经验丰富的经验丰富的研究员； 2）通过NYONRC进行正规教育研讨会和期刊俱乐部和实验室培训； 3）通过营养研究所的课程活动，4）补充临床和临床研究职责； 5）完成拟议的研究项目，从而成功地申请了独立资金。 公共卫生相关性：我们旨在提高脊柱肌肉萎缩（SMA）的基于证据的营养管理，这是一种因脊髓运动神经元丧失而标志着的不可治疗的遗传性儿科神经肌肉疾病。我们将研究疾病的严重程度，身体成分和能量消耗之间的关系，目的是为临床管理和营养调节的潜在作用提供影响，以影响疾病的自然病程。我们还将研究肌肉成像和电阻抗作为疾病进展的潜在生物标志物。这种生物标志物的发展对于SMA临床试验的加速至关重要。