ABSTRACT
This review focuses on the most recent data on biotherapeutic approaches, using DNA, RNA, recombinant proteins, or cells as therapeutic tools or targets for the treatment of neuromuscular diseases. Many of these novel technologies have now reached the clinical stage and have or are about to move to the market. Others, like genome editing are still in an early stage but hold great promise.
Subject(s)
Biological Therapy/methods , Neuromuscular Diseases/therapy , Animals , Antibodies, Monoclonal/therapeutic use , Autoimmune Diseases/therapy , Genetic Therapy , Humans , Motor Neurons/metabolism , Muscle, Skeletal/metabolism , RNA/therapeutic use , RNA Editing/geneticsABSTRACT
Thanks to the availability of computational grids and their middleware, a seamless access to computation and storage resources is provided to application developers and scientists. The Décrypthon project is one example of such a high performance platform. In this paper, we present the architecture of the platform, the middleware developed to facilitate access to several servers deployed in France, and the data center for integrating large biological datasets over multiple sites, supported by a new query language and integration of various tools. The SM2PH project represents an example of a biological application that exploits the capacities of the Décrypthon grid. The goal of SM2PH is a better understanding of mutations involved in human monogenic diseases, their impact on the 3D structure of the protein and the subsequent consequences for the pathological phenotypes.
Subject(s)
Computer Communication Networks , Medical Informatics Applications , Neuromuscular Diseases , Specialization , Genetic Diseases, Inborn , Humans , Software DesignABSTRACT
The purpose of this study was to characterize the alterations in muscle contractile (tension-pCa relationship) and biochemical (myosin heavy and light chains, troponin C content) properties in a hereditary motoneuron disease. The study was performed on wobbler mouse mutants which presented a neuronal degeneration. The time course of the disease was followed at 5 and 7 weeks in sternocleidomastoid (SCM) and soleus muscles. The wobbler disease was found to induce a shift from fast to slow myosin heavy-chain isoform expression in SCM and soleus muscles. The analysis of the myosin light-chain (MLC) composition revealed, for the SCM muscles, the appearance of the slow isoforms at 5 weeks and an increase in the regulatory MLC2 content at 7 weeks. A significant increase in the slow troponin C isoform content was found in both types of wobbler muscles at 7 weeks. The wobbler soleus and SCM muscles presented an age- and fiber-type-related atrophy, characterized by a decline in absolute maximal tension and fiber diameter. A decrease in calcium sensitivity was observed at 7 weeks for the soleus fibers and at both 5 and 7 weeks for the SCM. The results indicated fast-to-slow changes in contractile and biochemical properties of the wobbler soleus and SCM muscles, which occurred during the motoneuron degeneration process previously described in the wobbler pathology.
Subject(s)
Motor Neuron Disease/physiopathology , Muscle Contraction , Muscle, Skeletal/metabolism , Myofibrils/metabolism , Animals , Calcium/metabolism , In Vitro Techniques , Mice , Mice, Inbred C57BL , Mice, Neurologic Mutants , Motor Neuron Disease/metabolism , Motor Neuron Disease/pathology , Muscle Fibers, Fast-Twitch/metabolism , Muscle Fibers, Fast-Twitch/pathology , Muscle Fibers, Slow-Twitch/metabolism , Muscle Fibers, Slow-Twitch/pathology , Muscle, Skeletal/pathology , Myosin Heavy Chains/biosynthesis , Myosin Light Chains/biosynthesis , Protein Isoforms/biosynthesis , Troponin C/biosynthesisABSTRACT
Primates appeared to be a good model for investigating muscle contractile and biochemical properties, as well as EMG recordings. The purpose of our study was to examine the effects of microgravity on the contractile properties of the slow-type triceps and fast-type biceps muscles during the 14-day Bion 11 spaceflight.
Subject(s)
Muscle Fibers, Fast-Twitch/pathology , Muscle Fibers, Slow-Twitch/pathology , Muscular Atrophy/etiology , Space Flight , Weightlessness/adverse effects , Animals , Confined Spaces , Housing, Animal , Macaca mulatta , Male , Muscle Fibers, Fast-Twitch/metabolism , Muscle Fibers, Slow-Twitch/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Atrophy/metabolism , Muscular Atrophy/pathology , Myosin Heavy Chains/metabolismABSTRACT
Rats were submitted to 14 days of hindlimb suspension in order to examine the contractile and elastic properties of the soleus muscles under disuse conditions. The calcium/strontium activation properties, the maximal shortening velocity (V0), as well as the time behaviour of force transients following quick releases and the T1 curves characterizing the active part of the series elastic elements, were determined on single chemically skinned fibres. After the functional measurements, the fibres were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis in order to analyse both the myosin heavy (MHC) and light (MLC) chain isoforms. According to the MHC and MLC composition, two groups of fibres were defined after hindlimb suspension: a group of slow fibres expressing the slow set of both MHC and MLC isoforms, and a group of fast fibres co-expressing the slow and fast MHC and MLC isoforms with a predominant expression of the fast ones. For the first group, the contractile as well as the elastic properties were found to be close to those of control slow soleus fibres. For the second group, both contractile and elastic properties were modified insofar as they became close to those found in a fast muscle such as the extensor digitorum longus. We suggested that between the two populations found in the soleus muscle after hindlimb suspension the modifications in the contractile properties, as well as the alterations in the elastic characteristics, were concomitant to the changes in both MHC and MLC compositions.
