期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 41, 页码 16666-16671出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1202529109
关键词
SCH66336; laminopathy; cardiovascular disease; translational medicine
资金
- Progeria Research Foundation [PRFCLIN2007-01]
- Dana-Farber Cancer Institute Stop & Shop Pediatric Brain Tumor Program
- C.J. Buckley Fund
- Kyle Johnson Fund
- National Center for Research Resources, National Institutes of Health [MO1-RR02172, UL1 RR025758-01]
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a >= 50% increase, six experienced a >= 50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据