Skip to Main content Skip to Navigation
Journal articles

Danazol Treatment for Telomere Diseases

Abstract : Background - Genetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene. Methods - In a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point. Results - After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol--elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively. Conclusions - In our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.).
Document type :
Journal articles
Complete list of metadatas

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01390975
Contributor : Xavier Chard-Hutchinson <>
Submitted on : Wednesday, November 2, 2016 - 4:22:22 PM
Last modification on : Sunday, October 25, 2020 - 6:30:26 AM

Links full text

Identifiers

Citation

Stéphane Jouneau, Mallorie Kerjouan, Charles Ricordel. Danazol Treatment for Telomere Diseases. New England Journal of Medicine, Massachusetts Medical Society, 2016, 375 (11), pp.1095--1095. ⟨10.1056/NEJMoa1515319⟩. ⟨hal-01390975⟩

Share

Metrics

Record views

271