Joint Transnational Call 2013 (JTC2013)


Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) are rare neuromuscular diseases lacking diagnostic biomarkers. During the last decade, our teams have demonstrated that cell adhesion molecules (CAMs) play a crucial role in the formation of the nodes of Ranvier. Particularly, the complex Contactin-1/Caspr-1/Neurofascin controls paranode formation and the electrical insulation of the myelin. We found that antibodies to CAMs are detected in Guillain-Barré syndrome, and mediate demyelination. By contrast, autoantibodies in CIDP and MMN are only present in a small subgroup of patients. We recently demonstrated that a subgroup of CIDP patients show autoantibodies to Contactin-1 and Caspr-1. Of interest, this specific reaction could orientate their treatment. Here, we combined our efforts to elucidate how immune attack at nodes participates in CIDP severity and to test novel therapy. We propose to: Aim 1: Screen the reactivity to nodal antigens with the clinical features of CIDP and MMN patients. Aim 2: Identify new nodal and paranodal antigens using proteomic approaches: mass spectrometry and mammalian expression bank. Aim 3: Generate animal models of CIDP to study the pathological processes of CIDP. Aim 4: Use in vitro models (myelinating co-culture) to monitor the pathogenic effects of autoantibodies. Altogether, these results will advance tremendously the knowledge on the pathophysiology of CIDP and will help defining prognostic subgroups and guide novel therapeutic approaches.

  • Devaux, Jerôme (Coordinator)
    Aix-Marseille University, CNRS, UMR7286 [FRANCE]
  • Illa, Isabel
    Hospital Santa Creu i Santa Paula [SPAIN]
  • Peles, Elior
    Weizmann Institute fo Science [ISRAEL]