Safety and clinical outcome of tamoxifen in Duchenne muscular dystrophy.

Patients having Duchenne muscular dystrophy (DMD) are currently being treated with corticosteroids, which slow down disease progression at the expense of serious adverse effects. Tamoxifen is a pro-drug some of whose metabolites interact with the nuclear estrogen receptor, leading to anti-fibrotic and muscle-protective effects as has been demonstrated in a murine model of DMD. Here we report the results from a monocentric single arm prospective study in 13 ambulant boys aged 6-14 years with genetically confirmed DMD, aimed to assess the safety of tamoxifen and its impact on disease progression. Boys were treated for up to 3 years with 20 mg/day of oral tamoxifen, in addition to their ongoing corticosteroid treatment. For 8 of these patients, outcome was compared to an age- and performance-matched 12-month natural history dataset. The primary end point was the 6-minute walk test. Secondary end points were the NorthStar assessment, timed function tests, pulmonary function, the biomarker creatine phosphokinase and adverse effects. No adverse effects were noticed other than mild gynecomastia in 4 boys. Tamoxifen-treated patients retained motor and respiratory function, compared with a significant deterioration of age-matched historical control patients receiving corticosteroids only. These encouraging findings warrant a larger clinical trial to substantiate the use of tamoxifen in Duchenne muscular dystrophy.