Proposal for clinical investigation of tamoxifen in DMD boys

Urs Ruegg & Olivier Dorchies
University of Geneva, Switzerland

22nd June 2012

The proposal is to evaluate the use of tamoxifen, an orally active selective estrogen receptor modulator (SERM) in DMD, based on preliminary preclinical results in dystrophic (mdx5cv) mice, with the data awaiting publication. Tamoxifen presents an opportunity for repurposing since it is approved for other indications, has been widely used clinically for many years, is readily available and has an acceptable safety profile with generally few side effects at low doses. Additional pre-clinical studies using mdx and wild-type mice are currently on-going in an independent laboratory. The committee recommended that further pre-clinical experiments, addressing necrosis and inflammation, should be carried out in mdx mice, to help clarify the mechanism of the benefits of tamoxifen on dystrophic muscle and help in designing a clinical study. In addition, experiments using dogs are recommended to address the effects in pre-pubertal, growing animals. The metabolism and efficacy of the drug and optimal dosage, as well as possible adverse effects on growing tissues needs to be evaluated for pre-pubertal boys. If the further pre-clinical data confirm a marked benefit on the progression of dystropathology, a clinical trial could be undertaken with DMD boys. The planning of a clinical trial will require the input of experienced investigators in its design and execution.

12 Apr 2017