Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome
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- Leslie B. Gordon
- Departments of aAnesthesia,
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- Monica E. Kleinman
- Departments of aAnesthesia,
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- David T. Miller
- Medicine,
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- Donna S. Neuberg
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215;
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- Anita Giobbie-Hurder
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215;
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- Marie Gerhard-Herman
- Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
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- Leslie B. Smoot
- Cardiology,
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- Catherine M. Gordon
- Adolescent Medicine,
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- Robert Cleveland
- Radiology,
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- Brian D. Snyder
- Orthopedics,
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- Brian Fligor
- Otolaryngology and Communication Enhancement
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- W. Robert Bishop
- Merck Research Laboratories, Kenilworth, NJ 07033;
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- Paul Statkevich
- Merck Research Laboratories, Kenilworth, NJ 07033;
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- Amy Regen
- Dentistry,
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- Andrew Sonis
- Dentistry,
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- Susan Riley
- Physical Therapy and Occupational Therapy Services, and
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- Christine Ploski
- Physical Therapy and Occupational Therapy Services, and
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- Annette Correia
- Physical Therapy and Occupational Therapy Services, and
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- Nicolle Quinn
- Gastroenterology and Nutrition,
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- Nicole J. Ullrich
- Neurology Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115;
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- Ara Nazarian
- Center for Advanced Orthopaedic Studies, Department of Orthopaedics, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115; and
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- Marilyn G. Liang
- Medicine,
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- Susanna Y. Huh
- Medicine,
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- Armin Schwartzman
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215;
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- Mark W. Kieran
- Hematology-Oncology, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115;
Description
<jats:p> Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in <jats:italic>LMNA</jats:italic> 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. </jats:p>
Journal
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 109 (41), 16666-16671, 2012-09-24
Proceedings of the National Academy of Sciences
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Details 詳細情報について
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- CRID
- 1360574094665171200
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- ISSN
- 10916490
- 00278424
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- Data Source
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- Crossref