Impact of Farnesylation Inhibitors on Survival in Hutchinson-Gilford Progeria Syndrome
| العنوان: | Impact of Farnesylation Inhibitors on Survival in Hutchinson-Gilford Progeria Syndrome |
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| المؤلفون: | W. Ted Brown, Joan F. Brazier, Susan E. Campbell, Ralph B. D'Agostino, Mark W. Kieran, Monica E. Kleinman, Leslie B. Gordon, Joseph M. Massaro |
| المصدر: | Circulation. 130:27-34 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Oncology, Premature aging, Genetics, medicine.medical_specialty, Progeria, business.industry, Proportional hazards model, Hazard ratio, medicine.disease, Progerin, chemistry.chemical_compound, chemistry, Physiology (medical), Internal medicine, Medicine, Protein prenylation, Protein farnesylation, Lonafarnib, Cardiology and Cardiovascular Medicine, business |
| الوصف: | Background— Hutchinson-Gilford progeria syndrome is an ultrarare segmental premature aging disease resulting in early death from heart attack or stroke. There is no approved treatment, but starting in 2007, several recent single-arm clinical trials administered inhibitors of protein farnesylation aimed at reducing toxicity of the disease-producing protein progerin. No study assessed whether treatments influence patient survival. The key elements necessary for this analysis are a robust natural history of survival and comparison with a sufficiently large patient population that has been treated for a sufficient time period with disease-targeting medications. Methods and Results— We generated Kaplan–Meier survival analyses for the largest untreated Hutchinson-Gilford progeria syndrome cohort to date. Mean survival was 14.6 years. Comparing survival for treated versus age- and sex-matched untreated cohorts, hazard ratio was 0.13 (95% confidence interval, 0.04–0.37; P Conclusions— This study provides a robust untreated disease survival profile that can be used for comparisons now and in the future to assess changes in survival with treatments for Hutchinson-Gilford progeria syndrome. The current comparisons estimating increased survival with protein farnesylation inhibitors provide the first evidence of treatments influencing survival for this fatal disease. Clinical Trial Registration— URL: http://www.clinicaltrials.govTest . Unique Indentifiers: NCT00425607, NCT00879034, and NCT00916747. |
| تدمد: | 1524-4539 0009-7322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::ed7dbb205a6654f1c6ad30510fba3a80Test https://doi.org/10.1161/circulationaha.113.008285Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........ed7dbb205a6654f1c6ad30510fba3a80 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
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