Physical activity-correlated changes in plasma enzyme concentrations in fragile sarcolemmal muscular dystrophies

Abstract

STRUCTURED ABSTRACTBackground and ObjectivesMuscular dystrophies associated with decreased sarcolemma integrity lack validated clinical measures of sarcolemma fragility that can be used to assess disease progression and the effects of therapies designed to reduce sarcolemma fragility. We conducted a pilot study to test the hypothesis that physical activity leads to significant changes in muscle-derived plasma enzymes in participants with “fragile sarcolemmal muscular dystrophies” (FSMD).MethodsWe enrolled ambulatory individuals clinically affected with genetically confirmed FSMD neither taking anti-inflammatory medications nor having relevant co-morbidities for an inpatient study. Over five days, blood samples at 20 time points were obtained. Plasma enzymes alanine and aspartate aminotransferase (ALT, AST), creatine kinase (CK), and lactate dehydrogenase (LDH), all found in muscle, were measured before and after routine morning activities and motor function testing. Analysis of Z-transformed time series data led to feature and kinetic models that revealed activity-dependent feature and kinetic parameters.ResultsAmong the 11 enrolled participants, (LGMD Type 2B/R2 Dysferlin-related (4F/1M), LGMD Type 2L/R12 Anoctamin-5-related (3F/2M), LGMD Type 2I/R9 FKRP-related (1M)), plasma enzymes increased with activity. The average % change +/- SEM with morning activity across all participants was ALT 12.8 ± 2.8%, AST 11.6 ± 2.9%, CK 12.9 ± 2.8%, and LDH 12.2 ± 3.9%, suggesting the increases originate from the same stimulated source, presumably skeletal muscle. For ALT, AST, CK, and LDH, characteristic kinetic features include (a) elevated enzyme activities on arrival that decreased overnight; (b) a longer decay trend observed over the week, and (c) for ALT, AST, and CK, a similar decay trend observed with post-morning activity blood draws.DiscussionControlled activity-dependent changes in plasma ALT, AST, and CK on time scales of days to weeks can serve as common outcome measures for sarcolemma integrity and may be efficient and effective tools for monitoring disease progression and treatment efficacy for both individuals and patient populations. In addition, this study provides data that may benefit patient management as it can inform guidance on duration and type of activity that minimizes muscle damage.