Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy

Small non-coding microRNAs (miRNAs) are involved in the regulation of mRNA stability. Their features, including high stability and secretion to biofluids, make them attractive as potential biomarkers for diverse pathologies. This is the first study reporting miRNA as potential biomarkers for oculopharyngeal muscular dystrophy (OPMD), an adult-onset myopathy. We hypothesized that miRNA that is differentially expressed in affected muscles from OPMD patients is secreted to biofluids and those miRNAs could be used as biomarkers for OPMD. We first identified candidate miRNAs from OPMD-affected muscles and from muscles from an OPMD mouse model using RNA sequencing. We then compared the OPMD-deregulated miRNAs to the literature and, subsequently, we selected a few candidates for expression studies in serum and saliva biofluids using qRT-PCR. We identified 126 miRNAs OPMD-deregulated in human muscles, but 36 deregulated miRNAs in mice only (pFDR < 0.05). Only 15 OPMD-deregulated miRNAs overlapped between the in humans and mouse studies. The majority of the OPMD-deregulated miRNAs showed opposite deregulation direction compared with known muscular dystrophies miRNAs (myoMirs), which are associated. In contrast, similar dysregulation direction was found for 13 miRNAs that are common between OPMD and aging muscles. A significant age-association (p < 0.05) was found for 17 OPMD-deregulated miRNAs (13.4%), whereas in controls, only six miRNAs (1.4%) showed a significant age-association, suggesting that miRNA expression in OPMD is highly age-associated. miRNA expression in biofluids revealed that OPMD-associated deregulation in saliva was similar to that in muscles, but not in serum. The same as in muscle, miRNA expression levels in saliva were also found to be associated with age (p < 0.05). Moreover, the majority of OPMD-miRNAs were found to be associated with dysphagia as an initial symptom. We suggest that levels of specific miRNAs in saliva can mark muscle degeneration in general and dysphagia in OPMDFrench Muscular Dystrophy Association (AFM-Téléthon). Research grant to the eOPMD (European OPMD consortium, V.R. and B.G.M.v.E.)

Continued misuse of orphan drug legislation: a life-threatening risk for mexiletine.

Contains fulltext : 218857.pdf (Publisher’s version ) (Closed access

Overweight Is an Independent Risk Factor for Reduced Lung Volumes in Myotonic Dystrophy Type 1

Contains fulltext : 168011.PDF (publisher's version ) (Open Access)BACKGROUND: In this large observational study population of 105 myotonic dystrophy type 1 (DM1) patients, we investigate whether bodyweight is a contributor of total lung capacity (TLC) independent of the impaired inspiratory muscle strength. METHODS: Body composition was assessed using the combination of body mass index (BMI) and fat-free mass index. Pulmonary function tests and respiratory muscle strength measurements were performed on the same day. Patients were stratified into normal (BMI /= 25 kg/m2) groups. Multiple linear regression was used to find significant contributors for TLC. RESULTS: Overweight was present in 59% of patients, and body composition was abnormal in almost all patients. In overweight patients, TLC was significantly (p = 2.40x10-3) decreased, compared with normal-weight patients, while inspiratory muscle strength was similar in both groups. The decrease in TLC in overweight patients was mainly due to a decrease in expiratory reserve volume (ERV) further illustrated by a highly significant (p = 1.33x10-10) correlation between BMI and ERV. Multiple linear regression showed that TLC can be predicted using only BMI and the forced inspiratory volume in 1 second, as these were the only significant contributors. CONCLUSIONS: This study shows that, in DM1 patients, overweight further reduces lung volumes, as does impaired inspiratory muscle strength. Additionally, body composition is abnormal in almost all DM1 patients

Propagation disturbance of motor unit action potentials during transient paresis in generalized myotonia - A high-density surface EMG study

Patients with autosomal recessive generalized myotonia, or Pecker's disease, often suffer from a peculiar transient paresis, As yet, the relationship between this transient paresis and the defect in the gene encoding for a voltage gated Cl- channel protein in the muscle membrane of these patients is unclear. In order to gain a better understanding of the electrophysiological properties of the muscle fibre membrane in these generalized myotonia patients, we have studied transient paresis with a novel high-density surface EMG (sEMG) technique. We conclude that the transient paresis is explained by a deteriorating muscle membrane function, ending in conduction block and paresis, Multi-channel sEMG during the period of force decline in transient paresis shows a decrease in peak-peak amplitude of the motor unit action potentials from endplate towards tendon, This disturbance increases with time and place, indicating a deteriorating membrane function, and ends in a complete blocking of propagation within seconds. Spatiotemporally, this leads to a V-shaped sEMG pattern, In a more general sense, this contribution shows how spatiotemporal information, available through non-invasive high-density sERMG, may provide novel insights into electrophysiological aspects of membrane dysfunction