Changes in skeletal muscle qualities during enzyme replacement therapy in late‐onset type II glycogenosis: temporal and spatial pattern of mass vs. strength response

Abstract

Muscle quality is defined as muscle strength generated per unit muscle mass. If enzyme replacement therapy (ERT) has some effects on type II glycogenosis (GSDII) skeletal muscle pathology, we should be able to measure a change in strength and mass. We conducted a prospective study including 11 patients aged 54.2 ± 11.2 years, referring to a single institution and receiving ERT for ≥2 years. Median Walton score was 3 (2.5-6). Lower limb skeletal muscles were assessed by dynamometry and quantitative muscle MRI. Three segments (anterior thigh, posterior thigh, leg) were analysed separately. Clinical-MRI correlations were searched for at T0, T6/T8, and T18/24. Changes in lean and fat body composition were assessed by bioelectrical impedance analysis. We found that the anterior thigh showed the best therapeutic response, with an improvement in muscle quality (muscle mass: +7.5%, p = 0.035; strength: +45%, p = 0.002). BMI and lean body mass increased (p = 0.007). Patients with low BMI showed a better outcome. Intramuscular fat accumulation significantly progressed in spite of ERT (+3.7%, p = 0.001), especially in the poorly responsive posterior thigh muscles. Both clinical assessment and MRI revealed a definite improvement in the anterior thigh muscles. However, progression of intramuscular fat accumulation during ERT, as well as the limited responsiveness of posterior thigh muscles, suggests the necessity for early treatment intervention. The better outcome of patients with low BMI, if confirmed, may indicate that dietary protocols could be adopted as adjuvant measures to ERT in adult GSDII.

Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset Type II Glycogenosis?

“…We assessed muscle strength at lower limbs by a hand-held dynamometer (CITEC, CIT Techniques, The Netherlands) [12]. Resistance to exercise was assessed by a 6-MWT [18].…”

“…We considered our patients prospectively and repeatedly evaluated them during ERT as regards muscle strength, endurance, and mass; their clinical outcomes have been reported [12], and show that some cases behave as non responders. We investigated the following genetic polymorphisms: a) the I/D polymorphism of ACE; b) the R577X polymorphism of the α-actinin-3 (ACTN3); c) the G/C substitution in intron 7 of the Peroxisomal ProliferatorActivated Receptor-α (PPARα).…”

Imagerie et spectroscopie par résonance magnétique nucléaire du muscle strié squelettique

“…Très peu d'études longitudinales de la trophicité du muscle ont été réalisées sur des patients atteints de maladies neuro-musculaires. Un effet positif de l'enzymothérapie de substitution sur le volume musculaire des membres inférieurs a été observé chez des patients Pompe après seulement 6 mois de traitement (Ravaglia et al 2010). Suite à une période d'observation de 6 mois, l'aire de la section transversale du mollet de patients atteints de myosite à inclusions a perdu 6,5 %, alors qu'aucun changement n'a été observé chez des patients Charcot-Marie-Tooth 1A (Morrow et al 2015).…”

Skeletal Muscle Quantitative Nuclear Magnetic Resonance Imaging and Spectroscopy as an Outcome Measure for Clinical Trials (Part I)

“…Продолжительные исследования мышечной трофики были проведены лишь для некоторых НМБ. Положительный эффект ферментзаместительной те-рапии, оцениваемый по изменению объема мышц ног, наблюдался у больных с болезнью Помпе уже через 6 мес лечения [49]. Через 1 год наблюдения ППС икро-ножной мышцы уменьшалась на 6,5 % у больных мио-зитом с включениями, в то время как этот показатель не менялся у пациентов с болезнью Шарко-Мари-Тута 1А типа [50].…”