Duchenne muscular dystrophy (DMD) is a rare disease that affects about 1 in3500 to 1 in 6000 boys. Patients suffer from progressive muscle wasting,respiratory and cardiac impairments, and premature death. DMD is the mostfrequent hereditary muscular dystrophy. Currently, only symptomatic treatmentwith glucocorticoids is available; these have limited efficacy but many adverseeffects. The European Medical agency (EMA) and the US Federal drug agency(FDA) recognize the unmet medical need in DMD.Most current research on therapeutics of DMD focuses on correcting the genedefect. However, as there are more than 250 mutations in the human dystrophingene, this approach will treat only a small percentage of patients and will beexpensive, i.e. k€ 100-250 per patient per year as compared to tamoxifen (TAM)(about k€ 0.3). Using the mouse DMD model, our partners in Geneva Dorchieset al. have shown that TAM, given orally for periods of 2 or 15 months at dosesas low as 0.3 mg/kg/day, resulted in almost full recovery of force and structureof muscles. Very similar, yet unpublished, results have been obtained in thelaboratory of Professor D. Wells in London. TAM is likely the most efficaciouscompounds ever investigated in an animal model of DMD (for a comparison,see Ruegg 2013). TAM is a drug used since 1980 to treat breast cancer andhormonal disorders in pre-pubertal boys, too. There is broad clinical evidenceand reliable data suggesting a very good safety profile.Our aim is to investigate whether TAM treatment, compared to placebo, reducesthe disease progression in DMD patients. The project has been reviewed by EUfunded international TREAT-NMD (TACT) initiative. The project and studydesign has been discussed with DMD parent / patients organisations ofSwitzerland, Germany, the Netherlands, and the US who all strongly support theneed for such trial. The project will be presented to the European MedicinesAgency (EMA) to obtain an orphan drug designation (ODD) and to get formalscientific advice (by a specialised agency called EUDRAC). We plan a 48-weekplacebo controlled randomised clinical trial with 65 ambulant (6.5-10 year old)DMD patients (under stable standard treatment of care with glucocorticoids).Patients will receive daily 10 mg of TAM or placebo. The definitive primaryendpoint will be chosen after final scientific advice obtained from the EMA.Based on our power analyses, the highest effect size (and lowest patientnumber to be included) is the motor function measure (MFM) subscore D1(standing and transfers) which, therefore, is so far foreseen as primaryendpoint. Other considered clinical endpoints (and so far secondary) include theNorth Star Ambulant Assessment, timed function tests, and quantitative muscletesting. To investigate whether long-term 48-week TAM treatment can slowmuscle degeneration, we will measure the muscle fat fraction using quantitativemuscle magnetic resonance imaging (qMRI) (Bonati et al. 2015). We will closelycollaborate with ECRIN and its local partner, the Clinical Trial Unit (CTU) of theUniversity Hospital Basel. The CTU’s personal will manage the project, set upthe database (eCRF), monitor the trial and is responsible for statistical analysesof the study results. All partners contributing to this trial have broad experiencein caring for DMD patients and have already been involved in clinical studies.Together we care for about 150 patients fulfilling the inclusion criteria. Theinternational EU funded TREAT NMD initiative has set up a qualifiedinternational registry for patients with DMD. The national registries (D, A, CH)agreed to help to recruit patients for this trial.ReferencesDorchies OM et al. The anticancer drug tamoxifen counteracts the pathology ina mouse model of DMD. Am J Pathol. 182, 485-504 (2013)Ruegg UT. Pharmacological prospects in the treatment of DMD. Curr OpinNeurol. 26, 577-84 (2013)