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.

The Netherlands
Fast Skeletal Troponin Activation for Restoring Muscle Strength in Mouse Models of Nemaline Myopathy: a Molecular, Cellular, Metabolic and Functional Assessment

Project Coordinator

VU University Medical Center Laboratory for Physiology Institute for Cardiovascular Research
The Netherlands


Julien Gondin Aix Marseille University Marseille, France
Roberto Bottinelli Fondazione Salvatore Maugeri Pavia, Italy

Problem to be solved: No treatment is available for nemaline myopathy (NM), a rare and fatal muscle disease.
Background: A cardinal feature of NM is muscle weakness, caused by atrophy, impaired sarcomere contractility and alterations in energy pathways. This research program builds on our recent in vitro studies, funded by E-RARE1, which suggest that muscle strength in NM might be restored by fast skeletal troponin activation. Preclinical studies with fast skeletal troponin activators in live NM mice are now warranted.
Objective: Determine the efficacy of the fast skeletal troponin activator tirasemtiv in live NM mice.
Approach: Tirasemtiv will be tested in four NM mouse models: this allows us to cover a large spectrum of the disease. We will study its effect on muscle function, energy metabolism and NM biomarkers using non-invasive magnetic resonance imaging and spectroscopy, measurements of in vivo and ex vivo muscle strength and proteomic assessments of the involved signaling pathways. This combination allows for an in-depth analysis of the efficacy of tirasemtiv in NM mice
Innovation: The availability of (1) four NM mouse models, (2) high-end infrastructure to assess muscle - and whole body performance, and (3) a novel and promising drug, positions us ideally to tackle the problem posed.
Impact: Our research program is positioned at the level of basic science and its translation towards direct clinical application; its outcome might provide an impetus to preclinical studies in other disorders with muscle weakness.

E-Rare 2012 - Created by Toussaint Biger