Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson–Gilford progeria syndrome
| Autor: | Armin Schwartzman, Catherine M. Gordon, Amy Regen, Ara Nazarian, Nicolle Quinn, Nicole J. Ullrich, Donna Neuberg, Leslie B. Gordon, Marilyn G. Liang, Mark W. Kieran, W. Robert Bishop, Monica E. Kleinman, Andrew L. Sonis, Paul Statkevich, Robert H. Cleveland, Annette Correia, Marie Gerhard-Herman, Leslie B. Smoot, Brian Fligor, Christine Ploski, Brian D. Snyder, Susanna Y. Huh, Susan Riley, David T. Miller, Anita Giobbie-Hurder |
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| Rok vydání: | 2012 |
| Předmět: |
Diarrhea
Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Adolescent Pyridines Vomiting Pulse Wave Analysis Weight Gain Drug Administration Schedule LMNA chemistry.chemical_compound Progeria Piperidines Weight loss Internal medicine medicine Farnesyltranstransferase Humans Lonafarnib Enzyme Inhibitors Child Fatigue Multidisciplinary Dose-Response Relationship Drug integumentary system business.industry Farnesyltransferase inhibitor nutritional and metabolic diseases Biological Sciences medicine.disease Progerin Carotid Arteries Treatment Outcome Endocrinology chemistry Child Preschool Failure to thrive Cardiology Female medicine.symptom business Weight gain |
| Zdroj: | Proceedings of the National Academy of Sciences. 109:16666-16671 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1202529109 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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