Cysteamine: An old drug with new potential

Drug Discovery Today

Volumn 18, Issue 15-16, 2013, Pages 785-792

  Besouw, Martine ^a,b   Masereeuw, Rosalinde ^c   Van Den Heuvel, Lambert ^a,b,c   Levtchenko, Elena ^a,b  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^b UNIVERSITY OF LEUVEN   (Belgium)

^c RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTINEOPLASTIC AGENT; ASPARTATE AMINOTRANSFERASE; BRAIN DERIVED NEUROTROPHIC FACTOR; DOPAMINE; DOXORUBICIN; GLUTATHIONE; MERCAPTAMINE; PROTEIN GLUTAMINE GAMMA GLUTAMYLTRANSFERASE;

AREA UNDER THE CURVE; BLOOD BRAIN BARRIER; CELL PROLIFERATION; CYSTINOSIS; DEGENERATIVE DISEASE; DRUG BLOOD LEVEL; DRUG INDICATION; DRUG MEGADOSE; DUODENUM ULCER; ENZYME ACTIVITY; GENE EXPRESSION; HELA CELL; HUMAN; HUNTINGTON CHOREA; IN VITRO STUDY; MALARIA; MAXIMUM PLASMA CONCENTRATION; NONALCOHOLIC FATTY LIVER; NONHUMAN; OXIDATION; OXIDATIVE STRESS; PANCREAS CANCER; PARKINSON DISEASE; PHARMACODYNAMICS; PHARMACOKINETICS; RADIATION SICKNESS; REVIEW; SICKLE CELL ANEMIA; STOMACH ULCER; SURVIVAL;

ANIMALS; CYSTEAMINE; FATTY LIVER; HUMANS; NEURODEGENERATIVE DISEASES; RADIATION-PROTECTIVE AGENTS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84881145678     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2013.02.003     Document Type: Review

References (77)

1. M.B. Hoagland, and G.D. Novelli Biosynthesis of coenzyme A from phospho-pantetheine and of pantetheine from pantothenate J. Biol. Chem. 207 1954 767 773
2. R.M. Coloso Cysteamine dioxygenase: evidence for the physiological conversion of cysteamine to hypotaurine in rat and mouse tissues Adv. Exp. Med. Biol. 583 2006 25 36
3. R.J. Huxtable Physiological actions of taurine Physiol. Rev. 72 1992 101 163
4. P.D. Ray Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling Cell. Signal. 24 2012 981 990
5. D. Trachootham Redox regulation of cell survival Antioxid. Redox Signal. 10 2008 1343 1374
6. T.M. Jeitner, and D.A. Lawrence Mechanisms for the cytotoxicity of cysteamine Toxicol. Sci. 63 2001 57 64 (Pubitemid 32799024)
7. L.A. Smolin A comparison of the effectiveness of cysteamine and phosphocysteamine in elevating plasma cysteamine concentration and decreasing leukocyte free cystine in nephropathic cystinosis Pediatr. Res. 23 1988 616 620
8. R. Dohil The effect of food on cysteamine bitartrate absorption in healthy participants Clin. Pharmacol. Drug Dev. 1 2012 170 174
9. J.A. Gangoiti Pharmacokinetics of enteric-coated cysteamine bitartrate in healthy adults: a pilot study Br. J. Clin. Pharmacol. 70 2010 376 382
10. Z.M. Bacq Protection against X-rays and therapy of radiation sickness with beta-mercaptoethylamine Science 117 1953 633 636
11. J.B. Healy A trial of cystamine in radiation sickness Br. J. Radiol. 33 1960 512 514
12. H. Selye, and S. Szabo Experimental model for production of perforating duodenal ulcers by cysteamine in the rat Nature 244 1973 458 459
13. S. Szabo New molecular mechanisms of duodenal ulceration Ann. N. Y. Acad. Sci. 1113 2007 238 255 (Pubitemid 350015027)
14. S. Fukuhara Enhanced ghrelin secretion in rats with cysteamine-induced duodenal ulcers Am. J. Physiol. Gastrointest. Liver Physiol. 289 2005 G138 G145
15. S. Szabo, and S. Reichlin Somatostatin in rat tissues is depleted by cysteamine administration Endocrinology 109 1981 2255 2257 (Pubitemid 12252359)
16. K.R. McLeod Cysteamine-induced depletion of somatostatin in sheep: time course of depletion and changes in plasma metabolites, insulin, and growth hormone J. Anim. Sci. 73 1995 77 87
17. C.M. Yang Effects of cysteamine on growth performance, digestive enzyme activities, and metabolic hormones in broilers Poult. Sci. 85 2006 1912 1916 (Pubitemid 44583323)
18. G. Liu Effects of dietary supplementation with cysteamine on growth hormone receptor and insulin-like growth factor system in finishing pigs J. Agric. Food Chem. 56 2008 5422 5427 (Pubitemid 352039155)
19. M.C. Tse Effects of chronic cysteamine treatment on growth enhancement and insulin-like growth factor I and II mRNA levels in common carp tissues Br. J. Nutr. 96 2006 650 659 (Pubitemid 46470188)
20. W. Hassan Inhibition of erythrocyte sickling by cystamine, a thiol reagent Proc. Natl. Acad. Sci. U. S. A. 73 1976 3288 3292
21. W.Z. Ho Cystamine inhibits HIV type 1 replication in cells of monocyte/macrophage and T cell lineages AIDS Res. Hum. Retroviruses 11 1995 451 459
22. H.U. Bryant Cysteamine produces dose-related bidirectional immunomodulatory effects in mice J. Pharmacol. Exp. Ther. 249 1989 424 429 (Pubitemid 19144830)
23. P.J. Benke Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus Metabolism 39 1990 1278 1284
24. J. Brok Interventions for paracetamol (acetaminophen) overdose Cochrane Database Syst. Rev. 2006 CD003328
25. W.A. Gahl Cystinosis N. Engl. J. Med. 347 2002 111 121
26. J.G. Thoene Intracellular cystine depletion by aminothiols in vitro and in vivo J. Clin. Invest. 58 1976 180 189
27. M.J. Wilmer Cysteamine restores glutathione redox status in cultured cystinotic proximal tubular epithelial cells Biochim. Biophys. Acta 1812 2011 643 651
28. J.G. Thoene A review of the role of enhanced apoptosis in the pathophysiology of cystinosis Mol. Genet. Metab. 92 2007 292 298 (Pubitemid 350117712)
29. W.A. Gahl Cysteamine therapy for children with nephropathic cystinosis N. Engl. J. Med. 316 1987 971 977 (Pubitemid 17055375)
30. V.E. Kimonis Effects of early cysteamine therapy on thyroid function and growth in nephropathic cystinosis J. Clin. Endocrinol. Metab. 80 1995 3257 3261
31. T.C. Markello Improved renal function in children with cystinosis treated with cysteamine N. Engl. J. Med. 328 1993 1157 1162 (Pubitemid 23105753)
32. W.A. Gahl Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy Ann. Intern. Med. 147 2007 242 250 (Pubitemid 351664580)
33. A. Brodin-Sartorius Cysteamine therapy delays the progression of nephropathic cystinosis in late adolescents and adults Kidney Int. 81 2012 179 189
34. B.J. Corden Adverse reactions to oral cysteamine use in nephropathic cystinosis Dev. Pharmacol. Ther. 3 1981 25 30 (Pubitemid 11008485)
35. R. Dohil The evaluation and treatment of gastrointestinal disease in children with cystinosis receiving cysteamine J. Pediatr. 143 2003 224 230 (Pubitemid 37082957)
36. R. Dohil Esomeprazole therapy for gastric acid hypersecretion in children with cystinosis Pediatr. Nephrol. 20 2005 1786 1793 (Pubitemid 41722966)
37. M. Besouw The origin of halitosis in cystinotic patients due to cysteamine treatment Mol. Genet. Metab. 91 2007 228 233 (Pubitemid 46819126)
38. L. Krischock Drug-induced lupus and antiphospholipid syndrome associated with cysteamine therapy Nephrol. Dial. Transplant. 24 2009 1997 1999
39. Z.P. Ahmad Cystinosis and lupus erythematosus: coincidence or causation Pediatr. Nephrol. 25 2010 1543 1546
40. S. Rocha New-onset lupus nephritis in a kidney transplant recipient with cystinosis - differential diagnosis with cysteamine-induced lupus: case report Transplant. Proc. 43 2011 2265 2268
41. M.T. Besouw Cysteamine toxicity in patients with cystinosis J. Pediatr. 159 2011 1004 1011
42. M.T. Besouw Copper deficiency in cystinosis patients Pediatr. Nephrol. 27 2012 1634 1635
43. D.A. Beckman Developmental toxicity of cysteamine in the rat: effects on embryo-fetal development Teratology 58 1998 96 102 (Pubitemid 28493035)
44. C.B. Langman Effectiveness on white blood cell cystine levels and comparison of safety Clin. J. Am. Soc. Nephrol. 7 2012 1112 1120
45. J. Schulte, and J.T. Littleton The biological function of the Huntingtin protein and its relevance to Huntington's Disease pathology Curr. Trends Neurol. 5 2011 65 78
46. C.A. Ross, and S.J. Tabrizi Huntington's disease: from molecular pathogenesis to clinical treatment Lancet Neurol. 10 2011 83 98
47. C. Shults Huntington's disease: effect of cysteamine, a somatostatin-depleting agent Neurology 36 1986 1099 1102 (Pubitemid 16038591)
48. M.V. Karpuj Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington's disease brain nuclei Proc. Natl. Acad. Sci. U. S. A. 96 1999 7388 7393 (Pubitemid 29299671)
49. P. Kahlem Peptides containing glutamine repeats as substrates for transglutaminase-catalysed cross-linking: relevance to diseases of the nervous system Proc. Natl. Acad. Sci. U. S. A. 93 1996 14580 14585 (Pubitemid 26419010)
50. L. Munsie Mutant huntingtin causes defective actin remodeling during stress: defining a new role for transglutaminase 2 in neurodegenerative disease Hum. Mol. Genet. 20 2011 1937 1951
51. L. Lorand, and S.M. Conrad Transglutaminases Mol. Cell. Biochem. 58 1984 9 35
52. M.V. Karpuj Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine Nat. Med. 8 2002 143 149 (Pubitemid 34155125)
53. J.T. Pinto Measurement of sulfur-containing compounds involved in the metabolism and transport of cysteamine and cystamine. Regional differences in cerebral metabolism J. Chromatogr. B 877 2009 3434 3441
54. M. Lesort Cystamine inhibits caspase activity. Implications for the treatment of polyglutamine disorders J. Biol. Chem. 278 2003 3825 3830 (Pubitemid 36801110)
55. L. Revesz, and H. Modig Cysteamine-induced increase of cellular glutathione-level: a new hypothesis of the radioprotective mechanism Nature 207 1965 430 431
56. M. Borrell-Pages Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase J. Clin. Invest. 116 2006 1410 1424
57. R. Dubinsky, and C. Gray CYTE-I-HD: phase I dose finding and tolerability study of cysteamine (Cystagon) in Huntington's disease Mov. Disord. 21 2006 530 533
58. A.H. Schapira, and P. Jenner Etiology and pathogenesis of Parkinson's disease Mov. Disord. 26 2011 1049 1055
59. C. Gibrat, and F. Cicchetti Potential of cystamine and cysteamine in the treatment of neurodegenerative diseases Prog. Neuropsychopharmacol. Biol. Psychiatry 35 2011 380 389
60. C. Gibrat Cystamine prevents MPTP-induced toxicity in young adult mice via the up-regulation of the brain-derived neurotrophic factor Prog. Neuropsychopharmacol. Biol. Psychiatry 34 2010 193 203
61. L. Sun Effects of cysteamine on MPTP-induced dopaminergic neurodegeneration in mice Brain Res. 1335 2010 74 82
62. A. Pillai Cystamine prevents haloperidol-induced decrease of BDNF/TrkB signaling in mouse frontal cortex J. Neurochem. 107 2008 941 951
63. C.H. Shieh Potential antidepressant properties of cysteamine on hippocampal BDNF levels and behavioral despair in mice Prog. Neuropsychopharmacol. Biol. Psychiatry 32 2008 1590 1594
64. S.J. Tsai Cysteamine-related agents could be potential antidepressants through increasing central BDNF levels Med. Hypotheses 67 2006 1185 1188
65. J.C. Cohen Human fatty liver disease: old questions and new insights Science 332 2011 1519 1523
66. N. Chalasani The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association Hepatology 142 2012 1592 1609
67. R. Dohil Enteric-coated cysteamine for the treatment of paediatric non-alcoholic fatty liver disease Aliment. Pharmacol. Ther. 33 2011 1036 1044
68. R. Dohil The effect of cysteamine bitartrate on adiponectin multimerization in non-alcoholic fatty liver disease and healthy subjects J. Pediatr. 161 2012 639 645
69. G. Min-Oo Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus J. Exp. Med. 204 2007 511 524 (Pubitemid 46457075)
70. D. Cavallini Identification of pantethinase in horse kidney extract FEBS Lett. 1 1968 119 121
71. G. Min-Oo Cysteamine, the natural metabolite of pantetheinase, shows specific activity against Plasmodium Exp. Parasitol. 125 2010 315 324
72. G. Min-Oo Cysteamine, the molecule used to treat cystinosis, potentiates the antimalarial efficacy of artemisinin Antimicrob. Agents Chemother. 54 2010 3262 3270
73. J.R. Brawer The origin and composition of peroxidase-positive granules in cysteamine-treated astrocytes in culture Brain Res. 633 1994 9 20 (Pubitemid 24021238)
74. X.M. Wan Autophagy-mediated chemosensitization by cysteamine in cancer cells Int. J. Cancer 129 2011 1087 1095
75. H. Inano Inhibitory effects of WR-2721 and cysteamine on tumor initiation in mammary glands of pregnant rats by radiation Radiat. Res. 153 2000 68 74 (Pubitemid 30117085)
76. M. Tatsuta Inhibitory effect of prolonged administration of cysteamine on experimental carcinogenesis in rat stomach induced by N-methyl-N-nitro-N- nitrosoguanine Int. J. Cancer 41 1988 423 426 (Pubitemid 18080799)
77. T. Fujisawa Cysteamine suppresses invasion, metastasis and prolongs survival by inhibiting matrix metalloproteinases in a mouse model of human pancreatic cancer PLoS ONE 7 2012 e34437