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Drug Evaluations

The role of the farnesyltransferase inhibitor lonafarnib in the treatment of Progeria

, MD PhD, , MD PhD & , MD

Bibliography

  • Coppede F. Premature aging syndrome. Adv Exp Med Biol 2012;724:317-31
  • Dreesen O, Stewart CL. Accelerated aging syndromes, are they relevant to normal human aging? Aging (Albany NY) 2011;3:889-95
  • Hutchinson J. Congenital absence of hair and mammary glands with atrophic condition of the skin and its appendages in a boy whose mother had been almost wholly bald from alopecia areata from the age of six. Med Chir Trans 1886;69:473-77
  • Gilford H. Ateleiosis and progeria: continuous youth and premature old age. Br Med J 1904;2:914-18
  • Kieran MW, Gordon L, Kleinman M. New approaches to progeria. Pediatrics 2007;120:834-41
  • Gordon LB, Kleinman ME, Miller DT, et al. Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 2012;109:16666-71
  • Ullrich NJ, Kieran MW, Miller DT, et al. Neurologic features of Hutchinson-Gilford progeria syndrome after lonafarnib treatment. Neurology 2013;81:427-30
  • Gordon CM, Gordon LB, Snyder BD, et al. Hutchinson-Gilford progeria is a skeletal dysplasia. J Bone Miner Res 2011;26:1670-9
  • Gerhard-Herman M, Smoot LB, Wake N, et al. Mechanisms of premature vascular aging in children with hutchinson-gilford progeria syndrome. Hypertension 2011;59:92-7
  • Cleveland RH, Gordon LB, Kleinman ME, et al. A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome. Pediatr Radiol 2012;42:1089-98
  • Silvera VM, Gordon LB, Orbach DB, et al. Imaging characteristics of cerebrovascular arteriopathy and stroke in Hutchinson-Gilford progeria syndrome. AJNR Am J Neuroradiol 2013;34:1091-7
  • Nissan X, Blondel S, Navarro C, et al. Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA. Cell Rep 2012;2:1-9
  • De Sandre-Giovannoli A, Bernard R, Cau P, et al. Lamin a truncation in Hutchinson-Gilford progeria. Science 2003;300:2055
  • Eriksson M, Brown WT, Gordon LB, et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 2003;423:293-8
  • Young SG, Fong LG, Michaelis S. Prelamin A, Zmpste24, misshapen cell nuclei, and progeria–new evidence suggesting that protein farnesylation could be important for disease pathogenesis. J Lipid Res 2005;46:2531-58
  • Shackleton S, Smallwood DT, Clayton P, et al. Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype. J Med Genet 2005;42:e36
  • Reddy S, Comai L. Lamin A, farnesylation and aging. Exp Cell Res 2011;318:1-7
  • Ho CY, Lammerding J. Lamins at a glance. J Cell Sci 2012;125:2087-93
  • Lammerding J, Fong LG, Ji JY, et al. Lamins A and C but not lamin B1 regulate nuclear mechanics. J Biol Chem 2006;281:25768-80
  • Conneely KN, Capell BC, Erdos MR, et al. Human longevity and common variations in the LMNA gene: a meta-analysis. Aging Cell 2012;11:475-81
  • Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 2006;441:424-30
  • Fong LG, Ng JK, Meta M, et al. Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice. Proc Natl Acad Sci USA 2004;101:18111-16
  • Barrowman J, Hamblet C, Kane MS, Michaelis S. Requirements for efficient proteolytic cleavage of prelamin A by ZMPSTE24. PLoS One 2012;7:e32120
  • Smallwood DT, Shackleton S. Lamin A-linked progerias: is farnesylation the be all and end all? Biochem Soc Trans 2010;38:281-6
  • Lopez-Mejia IC, Vautrot V, De Toledo M, et al. A conserved splicing mechanism of the LMNA gene controls premature aging. Hum Mol Genet 2011;20:4540-55
  • Adam SA, Butin-Israeli V, Cleland MM, et al. Disruption of lamin B1 and lamin B2 processing and localization by farnesyltransferase inhibitors. Nucleus 2013;4:142-50
  • Davies BS, Barnes RH II, Tu Y, et al. An accumulation of non-farnesylated prelamin A causes cardiomyopathy but not progeria. Hum Mol Genet 2010;19:2682-94
  • Dechat T, Shimi T, Adam SA, et al. Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging. Proc Natl Acad Sci USA 2007;104:4955-60
  • Cao K, Capell BC, Erdos MR, et al. A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells. Proc Natl Acad Sci USA 2007;104:4949-54
  • Goldman R, Shumaker DK, Erdos MR, et al. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 2004;101(24):8963-8
  • Broedersz CP, Brangwynne CP. Nuclear mechanics: lamin webs and pathological blebs. Nucleus 2013;4:156-9
  • Wang Y, Ostlund C, Worman HJ. Blocking protein farnesylation improves nuclear shape abnormalities in keratinocytes of mice expressing the prelamin A variant in Hutchinson-Gilford progeria syndrome. Nucleus 2011;1:432-9
  • McClintock D, Gordon LB, Djabali K. Hutchinson-Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody. Proc Natl Acad Sci USA 2006;103:2154-9
  • Lans H, Hoeijmakers JH. Cell biology: ageing nucleus gets out of shape. Nature 2006;440:32-4
  • Csoka A, English S, Simkevich C, et al. Genome-scale expression profiling of Hutchinson-Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis. Aging Cell 2004;3:235-43
  • Agrawal AG, Somani RR. Farnesyltransferase inhibitor as anticancer agent. Mini Rev Med Chem 2009;9:638-52
  • Feldkamp MM, Gutmann DH, Guha A. Neurofibromatosis type 1: piecing the puzzle together. Can J Neurol Sci 1998;25:181-91
  • Yan N, Ricca C, Fletcher J, et al. Farnesyltransferase inhibitors block the neurofibromatosis type I (NF1) malignant phenotype. Cancer Res 1995;55:3569-75
  • Appels NM, Beijnen JH, Schellens JH. Development of farnesyl transferase inhibitors: a review. Oncologist 2005;10:565-78
  • Kohl NE, Conner MW, Gibbs JB, et al. Development of inhibitors of protein farnesylation as potential chemotherapeutic agents. J Cell Biochem Suppl 1995;22:145-50
  • Gibbs JB, Oliff A, Kohl NE. Farnesyltransferase inhibitors: ras research yields a potential cancer therapeutic. Cell 1994;77:175-8
  • Adjei AA. Farnesyltransferase inhibitors. Cancer Chemother Biol Response Modif 2005;22:123-33
  • Taveras AG, Kirschmeier P, Baum CM. Sch-66336 (sarasar) and other benzocycloheptapyridyl farnesyl protein transferase inhibitors: discovery, biology and clinical observations. Curr Top Med Chem 2003;3:1103-14
  • Liu M, Bryant MS, Chen J, et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res 1998;58:4947-56
  • Njoroge FG, Taveras AG, Kelly J, et al. (+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5, 6]cyclohepta[1,2-b]- pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamid e (SCH-66336): a very potent farnesyl protein transferase inhibitor as a novel antitumor agent. J Med Chem 1998;41:4890-902
  • Eskens FA, Awada A, Cutler DL, et al. Phase I and pharmacokinetic study of the oral farnesyl transferase inhibitor SCH 66336 given twice daily to patients with advanced solid tumors. J Clin Oncol 2001;19:1167-75
  • Kieran MW, Packer RJ, Onar A, et al. Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: a Pediatric Brain Tumor Consortium Study. J Clin Oncol 2007;25:3137-43
  • Awada A, Eskens FA, Piccart M, et al. Phase I and pharmacological study of the oral farnesyltransferase inhibitor SCH 66336 given once daily to patients with advanced solid tumours. Eur J Cancer 2002;38:2272-8
  • Adjei AA, Erlichman C, Davis JN, et al. A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res 2000;60:1871-7
  • Fong L, Ng J, Lammerding J, et al. Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J Clin Invest 2006;116:743-52
  • Wong NS, Morse MA. Lonafarnib for cancer and progeria. Expert Opin Investig Drugs 2012;21:1043-55
  • End DW, Smets G, Todd AV, et al. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res 2001;61:131-7
  • Zujewski J, Horak ID, Bol CJ, et al. Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer. J Clin Oncol 2000;18:927-41
  • Punt CJ, van Maanen L, Bol CJ, et al. Phase I and pharmacokinetic study of the orally administered farnesyl transferase inhibitor R115777 in patients with advanced solid tumors. Anticancer Drugs 2001;12:193-7
  • Rao S, Cunningham D, de Gramont A, et al. Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer. J Clin Oncol 2004;22:3950-7
  • Meta M, Yang SH, Bergo MO, et al. Protein farnesyltransferase inhibitors and progeria. Trends Mol Med 2006;12:480-7
  • Basso AD, Kirschmeier P, Bishop WR. Lipid posttranslational modifications. Farnesyl transferase inhibitors. J Lipid Res 2006;47:15-31
  • Yang SH, Bergo MO, Toth JI, et al. Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation. Proc Natl Acad Sci USA 2005;102:10291-6
  • Toth JI, Yang SH, Qiao X, et al. Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes. Proc Natl Acad Sci USA 2005;102:12873-8
  • Capell BC, Erdos MR, Madigan JP, et al. Inhibiting farnesylation of progerin prevents the characteristic nuclear blebbing of Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 2005;102:12879-84
  • Rusinol AE, Sinensky MS. Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors. J Cell Sci 2006;119:3265-72
  • Mounkes LC, Kozlov S, Hernandez L, et al. A progeroid syndrome in mice is caused by defects in A-type lamins. Nature 2003;423:298-301
  • Yang SH, Chang SY, Andres DA, et al. Assessing the efficacy of protein farnesyltransferase inhibitors in mouse models of progeria. J Lipid Res 2009;51:400-5
  • Yang SH, Chang SY, Ren S, et al. Absence of progeria-like disease phenotypes in knock-in mice expressing a non-farnesylated version of progerin. Hum Mol Genet 2010;20:436-44
  • Fong LG, Frost D, Meta M, et al. A protein farnesyltransferase inhibitor ameliorates disease in a mouse model of progeria. Science 2006;311:1621-3
  • Varga R, Eriksson M, Erdos MR, et al. Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 2006;103:3250-5
  • Yang SH, Meta M, Qiao X, et al. A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation. J Clin Invest 2006;116:2115-21
  • Capell BC, Olive M, Erdos MR, et al. A farnesyltransferase inhibitor prevents both the onset and late progression of cardiovascular disease in a progeria mouse model. Proc Natl Acad Sci USA 2008;105:15902-7
  • Merideth MA, Gordon LB, Clauss S, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med 2008;358:592-604
  • Gordon LB, McCarten KM, Giobbie-Hurder A, et al. Disease progression in Hutchinson-Gilford progeria syndrome: impact on growth and development. Pediatrics 2007;120:824-33
  • Arai Y, Takayama M, Abe Y, Hirose N. Adipokines and aging. J Atheroscler Thromb 2011;18:545-50
  • Varela I, Pereira S, Ugalde AP, et al. Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat Med 2008;14:767-72
  • Davies JM, Bailey MA, Griffin KJ, Scott DJ. Pulse wave velocity and the non-invasive methods used to assess it: complior, SphygmoCor, Arteriograph and Vicorder. Vascular 2012;20(6):342-9
  • Davies JI, Struthers AD. Beyond blood pressure: pulse wave analysis–a better way of assessing cardiovascular risk? Future Cardiol 2005;1:69-78
  • Chirinos JA. Arterial stiffness: basic concepts and measurement techniques. J Cardiovasc Transl Res 2012;5:243-55
  • Redheuil A, Yu WC, Wu CO, et al. Reduced ascending aortic strain and distensibility: earliest manifestations of vascular aging in humans. Hypertension 2010;55:319-26
  • Cruickshank K, Riste L, Anderson SG, et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation 2002;106:2085-90
  • Guardiani E, Zalewski C, Brewer C, et al. Otologic and audiologic manifestations of Hutchinson-Gilford progeria syndrome. Laryngoscope 2011;121(10):2250-5
  • The Progeria Research Foundation International Registry 2013
  • Olive M, Harten I, Mitchell R, et al. Cardiovascular pathology in Hutchinson-Gilford progeria: correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol 2010;30:2301-9
  • Scaffidi P, Misteli T. Lamin A-dependent nuclear defects in human aging. Science 2006;312:1059-63
  • McClintock D, Ratner D, Lokuge M, et al. The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS One 2007;2:e1269
  • Burtner CR, Kennedy BK. Progeria syndromes and ageing: what is the connection? Nat Rev Mol Cell Biol 2010;11:567-78
  • Cao K, Blair CD, Faddah DA, et al. Progerin and telomere dysfunction collaborate to trigger cellular senescence in normal human fibroblasts. J Clin Invest 2011;121:2833-44
  • Feldman EJ, Cortes J, DeAngelo DJ, et al. On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia. Leukemia 2008;22:1707-11
  • Sebti S, Hamilton AD. Inhibitors of prenyl transferases. Curr Opin Oncol 1997;9:557-61
  • Gordon LB, Cao K, Collins FS. Progeria: translational insights from cell biology. J Cell Biol 2012;199:9-13
  • Gonzalez JM, Pla D, Perez-Sala D, Andres V. A-type lamins and Hutchinson-Gilford progeria syndrome: pathogenesis and therapy. Front Biosci (Schol Ed) 2011;3:1133-46
  • de la Rosa J, Freije JM, Cabanillas R, et al. Prelamin A causes progeria through cell-extrinsic mechanisms and prevents cancer invasion. Nat Commun 2013;4:2268
  • Ibrahim MX, Sayin VI, Akula MK, et al. Targeting isoprenylcysteine methylation ameliorates disease in a mouse model of progeria. Science 2013;340:1330-3
  • Cenni V, Capanni C, Columbaro M, et al. Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria. Eur J Histochem 2012;55:e36
  • Graziotto JJ, Cao K, Collins FS, Krainc D. Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome: implications for normal aging and age-dependent neurodegenerative disorders. Autophagy 2011;8:147-51
  • Cao K, Graziotto JJ, Blair CD, et al. Rapamycin reverses cellular phenotypes and enhances mutant protein clearance in Hutchinson-Gilford progeria syndrome cells. Sci Transl Med 2011;3:89ra58
  • Blagosklonny MV. Progeria, rapamycin and normal aging: recent breakthrough. Aging (Albany NY) 2011;3:685-91

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