The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Danazol Treatment for Telomere Diseases
Open accessAbstract
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.).
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“The use of the androgen receptor agonist danazol in patients with aplastic anaemia with critically short telomeres improved their condition by increasing telomerase expression and lengthening telomeres. This provides support for a causative role of telomere length in this disease83.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [83]
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“androgen therapy, based on the clinical use of danazol, a synthetic testosterone, has been part of clinical practice for many years in the treatment of aplastic anaemia with some efficacy83”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [83]
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Citations
Cites
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
Telomeres and human disease: ageing, cancer and beyond
Blasco, M. A. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1656 · Cited by 1,434
Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
Artandi, S. E., Chang, S., Lee, S.-L., Alson, S., Gottlieb, G. J., Chin, L., & DePinho, R. A. (2000) · Nature · doi:10.1038/35020592 · Cited by 1,085
Heiss, N. S., Knight, S. W., Vulliamy, T. J., Klauck, S. M., Wiemann, S., Mason, P. J., Poustka, A., & Dokal, I. (1998) · Nature Genetics · doi:10.1038/ng0598-32 · Cited by 976
The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita
Vulliamy, T., Marrone, A., Goldman, F., Dearlove, A., Bessler, M., Mason, P. J., & Dokal, I. (2001) · Nature · doi:10.1038/35096585 · Cited by 960
Adult-onset pulmonary fibrosis caused by mutations in telomerase
Tsakiri, K. D., Cronkhite, J. T., Kuan, P. J., Xing, C., Raghu, G., Weissler, J. C., Rosenblatt, R. L., Shay, J. W., & Garcia, C. K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701009104 · Cited by 894
Calado, R. T., & Young, N. S. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0903373 · Cited by 814
Self-citationMutations in TERT, the Gene for Telomerase Reverse Transcriptase, in Aplastic Anemia
Yamaguchi, H., Calado, R. T., Ly, H., Kajigaya, S., Baerlocher, G. M., Chanock, S. J., Lansdorp, P. M., & Young, N. S. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa042980 · Cited by 723
Self-citationTelomere length and risk of incident cancer and cancer mortality
Willeit, P., Willeit, J., Mayr, A., Weger, S., Oberhollenzer, F., Brandstätter, A., Kronenberg, F., & Kiechl, S. (2010) · JAMA · doi:10.1001/jama.2010.897 · Cited by 484
Camitta, B. M., Thomas, E. D., Nathan, D., Rp, G., Kopecky, K., Rappeport, J., Santos, G., Gordon‐Smith, E. C., & Storb, R. F. (1979) · Blood · doi:10.1182/blood.v53.3.504.504 · Cited by 421
Cited by
Sorted by citations
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270
“Danazol is a synthetic steroid molecule that has telomereelongating capacity and has been used to antagonize accelerated telomere attrition (320).”
BackgroundTelomere dysfunction in ageing and age-related diseases
Rossiello, F., Jurk, D., Passos, J. F., & d’Adda di Fagagna, F. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00842-x · Cited by 754
Young, N. S. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1413485 · Cited by 762
Self-citationTelomeres: history, health, and hallmarks of aging
Chakravarti, D., LaBella, K. A., & DePinho, R. A. (2021) · Cell · doi:10.1016/j.cell.2020.12.028 · Cited by 637
“agents such as danazol (an antiestrogenic and antiprogestogenic) and 5a-dihydrotestosterone (an androgen), which can increase telomerase levels, are being tested in individuals with telomeropathies (Calado et al., 2009; Townsley et al., 2016).”
BackgroundHow I treat acquired aplastic anemia
Bacigalupo, A. P. (2017) · Blood · doi:10.1182/blood-2016-08-693481 · Cited by 435
Metadata
- Authors
- Townsley, D. M., Dumitriu, B., Liu, D., Biancotto, A., Weinstein, B., Chen, C., Hardy, N., Mihalek, A. D., Lingala, S., Kim, Y. J., Yao, J., Jones, E., Gochuico, B. R., Heller, T., Wu, C. O., Calado, R. T., Scheinberg, P., & Young, N. S.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-05-19
- Volume
- 374
- Issue
- 20
- Pages
- 1922-1931
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4968696
- OpenAlex
- W2394724717
- Cited by
- 415
- References
- 40
- Citations by year
- 2026: 23 · 2025: 32 · 2024: 36 · 2023: 46 · 2022: 32 · 2021: 45 · 2020: 46 · 2019: 41 · 2018: 49 · 2017: 46 · 2016: 19
- FWCI
- 41.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Institutes of Health (Z99 HL999999)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- danazol, telomere shortening, telomere length, telomerase, sex hormones, androgens, bone marrow failure syndromes, telomere maintenance, telomere elongation, hematologic response, liver cirrhosis, pulmonary fibrosis, drug safety, elevated liver enzymes, muscle cramps, treatment discontinuation
- MeSH terms
- Administration, Oral, Adolescent, Adult, Aged, Bone Marrow Diseases, Danazol, Estrogen Antagonists, Female, Hair Color, Humans, Liver Cirrhosis, Male, Middle Aged, Mutation, Prospective Studies, Pulmonary Fibrosis, Up-Regulation, Telomere, Telomerase, Young Adult
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