Nemaline myopathy (NM) is a rare and fatal neuromuscular disorder with an estimated prevalence of 1 in 50.000 live births. The main clinical feature of NM is muscle weakness, which impairs swallowing and causes severe respiratory problems. In children suffering from NM, the diaphragm is often severely affected, leading to suffocation. There is currently no treatment for NM, and efforts are directed at alleviating symptoms and compensating for disabilities as far as possible. Our E-Rare 1 project NEMMYOP has yielded important results on (1) the pathophysiology of muscle weakness in NM, on (2) new NM biomarkers, and on (3) in vitro effects of troponin activators on muscle fibres of NM patients. The insights gained in NEMMYOP have provided the first indications for a possible treatment for NM. To build upon this promising finding, TREAT-NEMMYOP will determine the efficacy of tirasemtiv, a fast skeletal troponin activator, in four NM mouse models. TREATNEMMYOP will make the next pivotal step towards clinical trials and future treatment of NM. To reach our aim, TREAT-NEMMYOP will assess the effect of tirasemtiv on (i) muscle function, (ii) energy metabolism and (iii) NM biomarkers. To obtain an in-depth evaluation of tirasemtiv efficacy, we will combine measurements of in vivo and ex vivo muscle strength, non-invasive magnetic resonance imaging (MRI) and spectroscopy with analysis of the involved signalling pathways and proteome. This also enables us to better understand the pathology of NM and the molecular mechanisms by which compounds such as tirasemtiv increase muscle strength in NM patients. TREAT-NEMMYOP is a powerful consortium of three academic groups and complementary collaborative partners, including the developer of tirasemtiv (Cytokinetics Inc.). The consortium has access to four unique NM mouse models and a high-end infrastructure that enables thorough assessment of muscle- and whole body performance. This makes TREAT-NEMMYOP well equipped to assess the efficacy of this highly promising treatment option for NM.