Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

Myotubularinopathies: common molecular mechanism and tissue specificity

Project Coordinator

IGBMC-ISERM U596 - UMR7104 Université Louis Pasteur Department of Molecular Biology


Alessandra Bolino Fondazione Centro San Raffaele del Monte Tabor DIBIT Milano, Italy
Bernard Payrastre ISERM U563 - CPTP - IFT30 Université Paul Sabatier Toulouse, France

Publications of the MTMpathies project

Major results of the project

Myotubularins (MTMs) define a large family of proteins with several members mutated in different neuromuscular disorders: demyelinating Charcot-Marie-Tooth (CMT) neuropathies (MTMR2 and MTMR13) and congenital myotubular/centronuclear (CNM) myopathy (MTM1). These rare diseases, called here myotubularinopathies, are characterized by early onset (neonatal or childhood) and by abnormal myelination of axons or disorganization of the skeletal muscle fibers, respectively. MTM1 and MTMR2 are proteins implicated in the regulation of lipids and intracellular membranes. The network gathered 3 partners with expertise in either lipid metabolism, the neuropathy or the myopathy diseases. We proposed to address the common molecular mechanism underlying the neuropathy and myopathy due to mutations in different myotubularins, and the basis of the tissue-specificity of these diseases. A better comprehension of the molecular basis of such severe diseases is a prerequisite for future therapeutic trials. Moreover, it is bringing novel disease markers that may
be used for diagnosis.

-We developed novel protocols to measure the level of the implicatd lipids in cells and tissues.
-We characterized a crucial and conserved role of the myotubularin proteins in the regulation
of phosphoinositides level (subset of lipids) and intracellular organization in different disease models.
-We provided strong evidence for a important role of the myotubularin MTMR2 protein in the formation/maintenance of the myelin, a sheath around neuron protrusions, and an unexpected role in neurons themselves. Importantly, tuning of the phosphoinositides rescued MTMR2- linked myelin defects, suggesting a possible future therapeutic approach.
-we identified a molecular defect at the basis of the congenital centronuclear myopathy, that explains why patients have the muscle weakness.
This program allowed a better comprehension of the mechanisms underlying normal muscle and neuron maturation and their dysregulation in neuromuscular diseases. It brings new markers for these rare neuromuscular disorders. It also linked two different myopathies and two neuropathies at the molecular level.

E-Rare 2012 - Created by Toussaint Biger