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.

Novel therapies for neuromuscular diseases with altered phosphoinositide metabolism

Project Coordinator

Hospital for Sick Children


Jocelyn Laporte IGBMC Illkirch, France
Volker Haucke Forschungsverbund Berlin e.V. Berlin, Germany
Bernard Payrastre INSERM Toulouse, France
Alessandra Bolino San Raffaele Scientific Institute Milan, Italy

This proposal will identify novel therapies for MTMopathies suitable for rapid clinical translation, test the concept of unified treatment for all MTMopathies, and lay the ground work for therapy development for the broader group of phosphoinoisitide (PIs) metabolism disorders. MTMopathies are rare neuromuscular genetic conditions caused by mutations in members of the myotubularin (MTMR) gene family. Specifically, mutations in MTM1 cause X-linked myotubular myopathy, and mutations in MTMR2, MTMR5 and MTMR13 are causes of autosomal recessive Charcot-Marie-Tooth Disease Type 4B. MTMopathies are characterized by severe muscle weakness and progressive disabilities (including wheelchair and ventilator dependence), as well as early mortality in some cases. Despite this high burden of morbidity and mortality, no therapies exist for this group of childhood disorders. Of note, MTMopathies are one subtype of an emerging group of neurogenetic diseases due to abnormalities in PIs metabolism that include forms of epilepsy, brain malformation syndrome, neurodevelopmental disease and neuropathies. MTMRs are phosphatases that function to dephosphorylate PIs at the 3-position. Mutations in MTMR genes result in abnormal levels of several PIs. Using the strategy of genetic inhibition of the kinases that regulate the PIs acted upon by MTMRs, we have shown in preclinical disease models that rebalancing PIs is a treatment strategy for MTMopathies. In this proposal, we will test the hypothesis that pharmacologic inhibition of these kinases can provide effective treatment for the diseases associated with MTM1 and MTMR2 mutations. To develop and translate therapies for MTMopathies based on the principle of PIs rebalancing via kinase inhibition.



E-Rare 2012 - Created by Toussaint Biger