M S-medecine Sciences最新文献

Centronuclear myopathies are rare congenital disorders characterized by muscle weakness and mislocalization of organelles. The main genes associated to these muscle diseases are MTM1, DNM2, BIN1 and RYR1. To date, no therapy is available. Nevertheless, tamoxifen, a pharmacological compound already used in clinics for breast cancer, showed beneficial effects on the muscle phenotypes in mouse models for centronuclear myopathies. Here, the effects of tamoxifen on muscle phenotypes will be compared in the various forms of this muscle disease.

The benefits of physical activity, on an organic and psychological level, have been demonstrated. In patients suffering from a neuromuscular disease, adapted physical activity and parasport are also means of combating a sedentary lifestyle which adds to that imposed by the disease. Whatever the motor skills of the subject, whether he walks or not, whether he has good upper limb strength or only minimal preserved distal function, a parasport can be practiced. Indeed certain disciplines are possible for patients with very weak motor functions. One of the missions of those involved in the life course of the person suffering from a neuromuscular disease is to talk about this subject. It is essential to make the patient, from a very young age, and their caregivers aware of this field of possibilities and its importance - all respecting possible contraindications or partial incapacities. Supporting a parasport practice means having to "get out of the hospital" and interact with local collaborators, to facilitate orientation, organize the initiation and introduction of the activity in the daily life of the patient. The time given to the patient and his caregivers to address this subject and guide them illustrates the overall care for this patient and the concern for his inclusion and his physical and mental health.

Tunneling nanotubes (TNTs) are open membranous protrusions that allow direct communication between distant cells. Recent research has revealed their significant biological roles, prompting a reassessment of many physiological and pathological processes, especially in the nervous system where TNT properties could play a key physiological role. TNT-like connections have been observed in the developing brain and are implicated in neurodegenerative diseases, brain cancers, as well as in other diseases, underscoring their importance in pathophysiological events. This review covers the key features of TNTs, including their structural properties, formation mechanisms, and detection challenges. We also explore their functions, focusing on the nervous system. The discovery of TNTs may lead to a reconsideration of brain function as a physically connected neuronal network, as proposed by Golgi, complementing Cajal's theory of neurons as separate entities.

The therapeutic management of autoimmune myasthenia gravis in children presents several particularities, which motivate the optimization of therapeutic management. On the one hand, corticosteroids are recommended as first-line immunosuppressive therapy, despite their significant adverse effects on growth, behavior, bone development, etc. On the other hand, in the absence of clinical trials in children, the place of promising new immunosuppressive therapies remains ill-defined. Rituximab is the non-steroidal immunosuppressant most widely used in France for autoimmune myasthenia gravis in children. Its use, without standardization of practices or monitoring of efficacy and safety, remains non-consensual. The aim of this study is to propose a new role for rituximab in the management of autoimmune myasthenia in children.

Genetic screening of rare diseases allows identification of the responsible gene(s) in about 50% of patients. The remaining cases are in a diagnostic deadlock as current knowledge fails to identify the correct gene or determine if the detected variant on the gene is pathogenic. These are named "variants of unknown significance" (VUS). In the case of neuromuscular diseases, the RYR1 gene is often implicated, with the majority of variants classified as VUS, requiring reliable classification to help patient diagnosis. Our project aims to create an efficient classification pipeline, integrating artificial intelligence, structural biology data, and functional analyses to enhance genetic diagnosis of RYR1-related diseases.

Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy are two ultra-rare lysosomal storage disorders resulting from loss-of-function mutations in the ASAH1 gene encoding for acid ceramidase (ACDase). ACDase deficiency leads to the intracellular accumulation of ceramides with an inflammatory response in tissues. These two diseases manifest differently but are part of a clinical continuum with variable severity affecting the nervous system and/or peripheral tissues, including the neuromuscular system. To date, no specific or curative treatments are available for patients affected by acid ceramidase deficiency. Here, we summarize the clinical features, enzyme function, mouse models and therapeutic perspectives for these allelic diseases.

Myotonic dystrophy type I (DM1) is a genetic disease characterized by a multisystemic RNA metabolism dysregulation and splicing toxicity. Numerous signaling pathways are deregulated, and especially AMPK, a key sensor and regulator of cellular metabolism. To restore AMPK signaling activity in DM1 muscle tissue and cells could improve mitochondrial biogenesis and dynamics, mitophagy and oxidative stress, energy production and, in fine, skeletal muscle tissue homeostasis.