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.
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.