Evaluation of body composition as a potential biomarker in spinal muscular atrophy

Baranello, Giovanni; Amicis, Ramona De; Arnoldi, Maria Teresa; Zanin, Riccardo; Mastella, Chiara; Masson, Riccardo; Alberti, Katia; Foppiani, Andrea; Battezzati, Alberto; Bertoli, Simona

doi:10.1002/mus.26823

Cited by 14 publications

(14 citation statements)

References 17 publications

(31 reference statements)

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“…Some patients with acceptable fat mass (FM) may plot as underweight since the BMI underestimates their body fat [ 50 , 51 , 57 ]. Relative to age and sex, these patients have a higher fat mass index (FMI) and lower lean tissue, which puts them at a higher risk of overweight status when compared to healthy children [ 46 , 54 , 57 , 58 , 59 ]. Across SMA groups, fat-free mass (FFM) and lean body mass (LBM) distribution are also different.…”

Section: Baseline Anthropometric Data and Energy Expenditure Of Sma Patientsmentioning

confidence: 99%

Metabolic Dysfunction in Spinal Muscular Atrophy

Deguise

Chehadé

Kothary

2021

IJMS

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Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder leading to paralysis, muscle atrophy, and death. Significant advances in antisense oligonucleotide treatment and gene therapy have made it possible for SMA patients to benefit from improvements in many aspects of the once devastating natural history of the disease. How the depletion of survival motor neuron (SMN) protein, the product of the gene implicated in the disease, leads to the consequent pathogenic changes remains unresolved. Over the past few years, evidence toward a potential contribution of gastrointestinal, metabolic, and endocrine defects to disease phenotype has surfaced. These findings ranged from disrupted body composition, gastrointestinal tract, fatty acid, glucose, amino acid, and hormonal regulation. Together, these changes could have a meaningful clinical impact on disease traits. However, it is currently unclear whether these findings are secondary to widespread denervation or unique to the SMA phenotype. This review provides an in-depth account of metabolism-related research available to date, with a discussion of unique features compared to other motor neuron and related disorders.

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Section: Baseline Anthropometric Data and Energy Expenditure Of Sma Patientsmentioning

confidence: 99%

Metabolic Dysfunction in Spinal Muscular Atrophy

Deguise

Chehadé

Kothary

2021

IJMS

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“…Because we do not have nontreated controls, the increase in BMI centiles in patients with SMA2 could also be due to the natural course of SMA itself like reported in previous studies that identified a high proportion of overweight in patients with SMA2. 2,12 Due to the high prevalence of increased fat mass in SMA 6,8,14 and the missing data of body composition, further studies need to analyze the effect of nusinersen on body composition including fat and muscle mass. Further, we did not evaluate confounding factors such as nutritional supplementation, high-caloric diet, and dysphagia in our study, which could lead to weight loss/gain in effected individuals.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Metabolic Effects of Nusinersen in Patients with Spinal Muscular Atrophy

Becker

Weiß

Günther

et al. 2021

Journal of Pediatric Neurology

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Nusinersen is the first disease-modifying therapy for spinal muscular atrophy (SMA), but there are few data on potential long-term endocrinological and metabolic systemic effects of this novel treatment as well as metabolic alterations in SMA itself. In this retrospective and multicentric study, we analyzed anthropometric, endocrinological, and motor function data of 81 pediatric and adult patients with SMA1 to 3 undergoing treatment with nusinersen. In 39 patients (51%), we observed a slight increase in body mass index (BMI) centiles under treatment with nusinersen, especially in patients with SMA2 and in pediatric patients between 3.1 and 12 years. A correlation to the SMN2 copy number or motor function was not found. Additionally, length centiles decreased significantly under treatment. The results of longitudinal endocrinological assessments were interpreted as not clinically significant in most patients; in three patients, the signs of an altered glucose metabolism were present. Our study indicates a putative effect of treatment with nusinersen on BMI, which might be due to a conjoint effect of weight gain and reduction of height velocity, without evidence of correlation to increased muscle function. Further studies need to address specific effects of targeted therapies such as nusinersen or onasemnogene abeparvovec on body composition including fat and muscle mass.

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“…A total body image was obtained, with computer‐generated estimates for the percentage of total body fat, LBM, and bone. Similar to a recent study of body composition in SMA patients, fat‐free mass was calculated as the sum of lean mass and bone mineral content divided by total body mass and expressed as a percentage 31 . Whole‐body oxygen consumption (VO 2 ) relative to LBM was also calculated as absolute VO 2 at peak exercise (mL/min) divided by LBM (kg) from DEXA.…”

Section: Methodsmentioning

confidence: 99%

Diminished muscle oxygen uptake and fatigue in spinal muscular atrophy

Montes

Goodwin

McDermott

et al. 2021

Ann Clin Transl Neurol

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Objective To estimate muscle oxygen uptake and quantify fatigue during exercise in ambulatory individuals with spinal muscular atrophy (SMA) and healthy controls. Methods Peak aerobic capacity (VO2peak) and workload (Wpeak) were measured by cardiopulmonary exercise test (CPET) in 19 ambulatory SMA patients and 16 healthy controls. Submaximal exercise (SME) at 40% Wpeak was performed for 10 minutes. Change in vastus lateralis deoxygenated hemoglobin, measured by near‐infrared spectroscopy, determined muscle oxygen uptake (ΔHHb) at rest and during CPET and SME. Dual energy X‐ray absorptiometry assessed fat‐free mass (FFM%). Fatigue was determined by percent change in workload or distance in the first compared to the last minute of SME (FatigueSME) and six‐minute walk test (Fatigue6MWT), respectively. Results ΔHHb‐PEAK, ΔHHb‐SME, VO2peak, Wpeak, FFM%, and 6MWT distance were lower (P < 0.001), and Fatigue6MWT and FatigueSME were higher (P < 0.001) in SMA compared to controls. ΔHHb‐PEAK correlated with FFM% (r = 0.50) and VO2peak (r = 0.41) only in controls. Only in SMA, Fatigue6MWT was inversely correlated with Wpeak (r = −0.69), and FatigueSME was inversely correlated with FFM% (r = −0.55) and VO2peak (r = −0.69). Interpretation This study provides further support for muscle mitochondrial dysfunction in SMA patients. During exercise, we observed diminished muscle oxygen uptake but no correlation with aerobic capacity or body composition. We also observed increased fatigue which correlated with decreased aerobic capacity, workload, and body composition. Understanding the mechanisms underlying diminished muscle oxygen uptake and increased fatigue during exercise in SMA may identify additional therapeutic targets that rescue symptomatic patients and mitigate their residual disease burden.

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Evaluation of body composition as a potential biomarker in spinal muscular atrophy

Cited by 14 publications

References 17 publications

Metabolic Dysfunction in Spinal Muscular Atrophy

Metabolic Dysfunction in Spinal Muscular Atrophy

Evaluation of Metabolic Effects of Nusinersen in Patients with Spinal Muscular Atrophy

Diminished muscle oxygen uptake and fatigue in spinal muscular atrophy

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