Update on the “Myasthenia” parallel symposia
 
About fifty myasthenia specialists took part in the Congress of Myology 2005 (in all representing 9 European countries as well as a team from the United States). More than 40 posters on the subject were discussed. And the main points to come out of the congress? The dynamism of the European Myasthenia network, the advances at the level of the physiopathological mechanisms of myasthenia and the identification of promising therapeutic leads.
 
Prof Eymard (Institute of Myology) took stock of the new mutations in congenital myasthenias in an exposé which demonstrated the importance of the congenital myasthenia network for grouping together medical, biological, electrophysiological and genetic information about this group of rare and little-known disorders.

Advances in autoimmune myasthenia were presented by Dr Sonia Berrih-Aknin who explained the causes of thymic pathology in young patients. With her team at Plessis Robinson (near Paris), she demonstrated a severe defect of regulatory T cells which could explain the pro-inflammatory environment of the thymus of patients. Using an approach by DNA chip, this team also discovered that a chemokine, CXCL13, is overproduced in the thymus cells of patients. These cells attract B cells in great numbers which, in the pr?????=???Aeesence of the antigene and the inflammatory environment, can explain the production of anti-RACh antibodies, whose pathogenic role is well-known. Dr Berrih-Aknin emphasised the major role of the AFM in the structuring of myasthenia research : 2 European contracts had been obtained, thus enabling the personnel of a dozen European myasthenia research teams to be increased. Another important discovery reported by Dr Berrih-Aknin was that by the British team of Prof A.Vincent who highlighted the existence of a second antigene, the MuSK molecule, against which certain patients produce an autoimmune reaction.

 
Prof Sara Fuchs, of the Weizmann Institute (Israel), explained why injection of the RACh of torpedo made it possible to obtain a model similar to the human disease in the rat. Using this model and DNA chips, Prof Fuchs and her team highlighted the role of another chemokine, IP10, in the pathogenic mechanisms of myasthenia. In addition, this team showed the advantage of adapting phosphodiesterase expression (by pentoxifylline) to improve disease symptoms in the rat. .
 
Finally, Prof Mona Soreq, of the Hebraic University of Jerusalem, emphasised the role played by acetylcholinesterase, not only at the level of the neuromuscular junction but also in inflammation, by insisting on a particular form  of acetylcholinesterase, the R (Readthrough) form, linked to stress. Prof Soreq also presented promising results of a phase I clinical trial in patients.

 

 

Limb girdle muscular dystrophies (LGMDs) represent a group of neuromuscular diseases characterised by damage to the muscles of the pelvis (pelvic girdle) and shoulders (scapular girdle), for which no curative treatment exists at present. In the framework of their genetic research at Généthon (Evry), Isabelle Richard and her team have developed two gene therapy trials in mice models of LGMD2A (calpainopathy) and LGMD2D (α-sarcoglycanopathy). The viral vector AAV1 (adeno associated virus) coupled either with the calpain gene or with the α-sarcoglycan gene was injected intra-arterially one of the legs of the mouse models. In both cases, the deficient protein expression was restored and the motor capacities of the legs were re-established. These very encouraging results have prompted the Généthon researchers to propose two phase I clinical trial projects for calpainopathy and α-sarcoglycanopathy.