Safety and clinical outcome of tamoxifen in Duchenne muscular dystrophy

Reuven Tsabari; Elana Simchovitz; Eran Lavi; Osnat Eliav; Ran Avrahami; Shmuel Ben-Sasson; Talya Dor

doi:10.1016/j.nmd.2021.05.005

Safety and clinical outcome of tamoxifen in Duchenne muscular dystrophy

Neuromuscul Disord. 2021 Sep;31(9):803-813. doi: 10.1016/j.nmd.2021.05.005. Epub 2021 Jun 5.

Authors

Reuven Tsabari¹, Elana Simchovitz², Eran Lavi³, Osnat Eliav⁴, Ran Avrahami⁴, Shmuel Ben-Sasson⁵, Talya Dor⁶

Affiliations

¹ Pediatric Pulmonology Unit, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Israel.
² Physiotherapy Department, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Israel.
³ Pediatric Endocrinology Unit, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Israel.
⁴ Pediatric Neurology Unit, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Israel.
⁵ Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada (IMRIC), The Faculty of Medicine, Hebrew University of Jerusalem, Israel.
⁶ Physiotherapy Department, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Israel. Electronic address: talyad@hadassah.org.il.

PMID: 34304968
DOI: 10.1016/j.nmd.2021.05.005

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02835079.

Keywords: Duchenne muscular dystrophy; Tamoxifen.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adrenal Cortex Hormones / therapeutic use
Child
Disease Progression
Humans
Israel
Male
Motor Activity / drug effects
Muscular Dystrophy, Duchenne / drug therapy*
Prospective Studies
Selective Estrogen Receptor Modulators / therapeutic use*
Tamoxifen / therapeutic use*
Treatment Outcome
Walk Test

Substances

Adrenal Cortex Hormones
Selective Estrogen Receptor Modulators
Tamoxifen

Associated data

ClinicalTrials.gov/NCT02835079