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  • 1 Semmelweis Egyetem, Általános Orvostudományi Kar II. Belgyógyászati Klinika Budapest Szentkirályi u. 46. 1088
  • 2 MTA-SE Molekuláris Medicina Kutatócsoport Budapest
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A lizoszómák enzimeinek hiánya vagy csökkent működése, illetve az enzimek és szubsztrátjaik transzportzavara okozza a lizoszomális tárolási rendellenességeket. A le nem bontott makromolekulák felhalmozódnak, károsítják a sejteket, ami különböző klinikai tüneteket okozhat. Ma megközelítőleg 40 különböző tárolási betegséget különítünk el. Kezelésükben az elmúlt évtizedekig csak szupportív módszereket alkalmaztunk. Az elmúlt évtizedek kutatási eredményei kiszélesítették a terápiás lehetőségeket. A közlemény bemutatja a lizoszomális tárolási betegségeket, áttekinti a terápiás lehetőségeket jelentő enzimpótló kezelést, a szubsztrátcsökkentő terápiát, a csontvelő-átültetést, és felveti a jövő lehetséges kezelését, az őssejtbeültetést és a génterápiát.

  • Tulassay Zs.: A lysosoma alterációk klinikai vonatkozásai. Magy. Belorv. Arch., 1972, 24 , 57–65.

    Tulassay Zs. , 'A lysosoma alterációk klinikai vonatkozásai ' (1972 ) 24 Magy. Belorv. Arch. : 57 -65.

    • Search Google Scholar
  • Grabowski, G.: Lysosomale Speichererkrankungen. In Harrisons: Innere Medizin, 15. Auflage, Berlin, McGraw–Hill, 2001, 2480–2481.

    Grabowski G. , '', in Harrisons: Innere Medizin , (2001 ) -.

  • De Duve, C., Wattiaux, R.: Function of lysosomes. Annu. Rev. Physiol., 1966, 28 , 435–492.

    Wattiaux R. , 'Function of lysosomes ' (1966 ) 28 Annu. Rev. Physiol. : 435 -492.

  • Neufeld, E. F, Muenzer, J.: The mucopolysaccharidoses. In: Scriver, C. R, Beaudet, A. L., Sly, W. S. és mtsai (szerk.) The metabolic and molecular bases of inherited disease. 8th ed. New York, McGraw–Hill, 2001, 3421–3452.

    Muenzer J. , '', in The metabolic and molecular bases of inherited disease , (2001 ) -.

  • Desnick, R. J.: Enzyme therapy in genetic diseases. II. New York, Alan, R. Liss, 1980.

    Desnick R. J. , '', in Enzyme therapy in genetic diseases. II. , (1980 ) -.

  • Desnick, R. J., Bernlohr, R. W., Krivit, W.: Enzyme therapy in genetic diseases. Birth defects. New York, The National Fundation, 1973.

    Krivit W. , '', in Enzyme therapy in genetic diseases. Birth defects , (1973 ) -.

  • Brady, R. O., Murray, G. J., Barton, N. W.: Modifying exogenous glucocerebrosidase for effective replacement therapy in Gaucher’s disease. J. Inherit. Metab. Dis., 1994, 17 , 510–519.

    Barton N. W. , 'Modifying exogenous glucocerebrosidase for effective replacement therapy in Gaucher’s disease ' (1994 ) 17 J. Inherit. Metab. Dis. : 510 -519.

    • Search Google Scholar
  • Rohrbach, M., Clarke, J. T. R.: Treatment of lysosomal storage disorders. Progress with enzyme replacement therapy. Drugs, 2007, 67 , 2697–2716.

    Clarke J. T. R. , 'Treatment of lysosomal storage disorders. Progress with enzyme replacement therapy ' (2007 ) 67 Drugs : 2697 -2716.

    • Search Google Scholar
  • Brady, R. O., Tallman, J. F., Johnson, W. G. és mtsai: Replacement therapy for inherited enzyme deficiency: use of purified ceremide-trihexosidase in Fabry’s disease. N. Eng. J. Med., 1973, 289 , 9–14.

    Johnson W. G. , 'Replacement therapy for inherited enzyme deficiency: use of purified ceremide-trihexosidase in Fabry’s disease ' (1973 ) 289 N. Eng. J. Med. : 9 -14.

    • Search Google Scholar
  • Barton, N. W., Brady, R. O., Dambrosia, J. M. és mtsai: Replacement therapy for inherited enzyme deficiency: macrophage-targeted glucocerebrosidase for Gaucher’s disease. N. Eng. J. Med., 1991, 324 , 1464–1670.

    Dambrosia J. M. , 'Replacement therapy for inherited enzyme deficiency: macrophage-targeted glucocerebrosidase for Gaucher’s disease ' (1991 ) 324 N. Eng. J. Med. : 1464 -1670.

    • Search Google Scholar
  • Schiffmann, R., Heyes, M. P., Aerts, J. M. és mtsai: Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher’s disease. Ann. Neurol., 1997, 42 , 613–621.

    Aerts J. M. , 'Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher’s disease ' (1997 ) 42 Ann. Neurol. : 613 -621.

    • Search Google Scholar
  • Altarescu, G., Hill, S., Wiggs, E. és mtsai: The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher’s disease. J. Pediatr., 2001, 138 , 539–547.

    Wiggs E. , 'The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher’s disease ' (2001 ) 138 J. Pediatr. : 539 -547.

    • Search Google Scholar
  • Eng, C. M., Guffon, N., Wilcox, W. R. és mtsai; International Collaborative Fabry Disease Study Group: Safety and efficacy of recombinant human alfa-galactosidase A: replacement therapy in Fabry’s diseas. N. Eng. J. Med., 2001, 345 , 9–16.

    Wilcox W. R. , 'Safety and efficacy of recombinant human alfa-galactosidase A: replacement therapy in Fabry’s diseas ' (2001 ) 345 N. Eng. J. Med. : 9 -16.

    • Search Google Scholar
  • Vedder, A. C., Linthorst, G. E., van Breemen, M. J. és mtsai: The Dutch Fabry cohort: diversity of clinical manifestation and Gb3 levels. J. Inherit. Metab. Dis., 2007, 30 , 68–78.

    Breemen M. J. , 'The Dutch Fabry cohort: diversity of clinical manifestation and Gb3 levels ' (2007 ) 30 J. Inherit. Metab. Dis. : 68 -78.

    • Search Google Scholar
  • Banikazemi, M., Bultas, J., Waldek, S. és mtsai: Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. Ann. Intern. Med., 2007, 146 , 77–86.

    Waldek S. , 'Agalsidase-beta therapy for advanced Fabry disease: a randomized trial ' (2007 ) 146 Ann. Intern. Med. : 77 -86.

    • Search Google Scholar
  • Wraith, J. E., Clarke, L. A., Beck, M. és mtsai: Enzyme replacement therapy for mucopoly-saccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J. Pediatr., 2004, 144 , 581–588.

    Beck M. , 'Enzyme replacement therapy for mucopoly-saccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase) ' (2004 ) 144 J. Pediatr. : 581 -588.

    • Search Google Scholar
  • Harmatz, P., Whitley, C. B., Waber, L. és mtsai: Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux–Lamy syndrome). J. Pediatr., 2004, 144 , 574–580.

    Waber L. , 'Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux–Lamy syndrome) ' (2004 ) 144 J. Pediatr. : 574 -580.

    • Search Google Scholar
  • Muenzer, J., Wraith, J. E., Beck, M. és mtsai: A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet. Med., 2006, 8 , 465–473.

    Beck M. , 'A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome) ' (2006 ) 8 Genet. Med. : 465 -473.

    • Search Google Scholar
  • Van den Hout, H. M., Hop, W., van Diggelen, O. P. és mtsai: The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatrics, 2003, 112 , 332–340.

    Diggelen O. P. , 'The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature ' (2003 ) 112 Pediatrics : 332 -340.

    • Search Google Scholar
  • Kishnani, P. S., Hwu, W. L., Mandel, H. és mtsai; Infantile-Onset Pompe Disease Natural History Study Group: A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe’s disease. J. Pediatr., 2006, 148 , 671–676.

    Mandel H. , 'A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe’s disease ' (2006 ) 148 J. Pediatr. : 671 -676.

    • Search Google Scholar
  • Kishnani, P. S., Corzo, D., Nicolino, M. és mtsai: Recombinant human acid (alpha)-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology, 2007, 68 , 99–109.

    Nicolino M. , 'Recombinant human acid (alpha)-glucosidase: major clinical benefits in infantile-onset Pompe disease ' (2007 ) 68 Neurology : 99 -109.

    • Search Google Scholar
  • Kakkis, E. D., Schuchman, E., He, X. és mtsai: Enzyme replacement therapy in feline mucopolysaccharidosis. I. Mol. Genet. Metab., 2001, 72 , 199–208.

    He X. , 'Enzyme replacement therapy in feline mucopolysaccharidosis. I ' (2001 ) 72 Mol. Genet. Metab. : 199 -208.

    • Search Google Scholar
  • Capablo, J. L., Franco, R., de Cabazon, A. S. és mtsai: Neurologic improvement in a type 3 Gaucher’s disease treated with imiglucerase/miglustat combination. Epilepsia, 2007, 48 , 1406–1408.

    Cabazon A. S. , 'Neurologic improvement in a type 3 Gaucher’s disease treated with imiglucerase/miglustat combination ' (2007 ) 48 Epilepsia : 1406 -1408.

    • Search Google Scholar
  • Bembi, B., Marchetti, F., Guerci, V. I. és mtsai: Substrate reduction therapy in the infantile form of Tay–Sachs disease. Neurology, 2006, 66 , 278–280.

    Guerci V. I. , 'Substrate reduction therapy in the infantile form of Tay–Sachs disease ' (2006 ) 66 Neurology : 278 -280.

    • Search Google Scholar
  • Zervas, M., Somers, K. L., Thrall, M. A. és mtsai: Critical role for glycosphingolipids in Niemann–Pick disease type C. Curr. Biol., 2001, 11 , 1283–1287.

    Thrall M. A. , 'Critical role for glycosphingolipids in Niemann–Pick disease type C ' (2001 ) 11 Curr. Biol. : 1283 -1287.

    • Search Google Scholar
  • Patterson, M. C., Vecchio, D., Prady, H. és mtsai: Miglustat for treatment of Niemann–Pick C disease: a randomised controlled study. Lancet Neurol., 2007, 6 , 765–772.

    Prady H. , 'Miglustat for treatment of Niemann–Pick C disease: a randomised controlled study ' (2007 ) 6 Lancet Neurol. : 765 -772.

    • Search Google Scholar
  • Piotrowska, E., Jakóbkiewicz-Banecka, J., Baranska, S. és mtsai: Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. Eur. J. Hum. Gen., 2006, 14 , 846–852.

    Baranska S. , 'Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses ' (2006 ) 14 Eur. J. Hum. Gen. : 846 -852.

    • Search Google Scholar
  • Roberts, A. L. K., Rees, M. H., Kleje, S. és mtsai: Improvement in behaviour after substrate deprivation therapy with rhodamin B in a mouse model of MPS IIIA. Mol. Gen. Metabol., 2007, 92 , 115–121.

    Kleje S. , 'Improvement in behaviour after substrate deprivation therapy with rhodamin B in a mouse model of MPS IIIA ' (2007 ) 92 Mol. Gen. Metabol. : 115 -121.

    • Search Google Scholar
  • Wegrzyn, G., Jakóbkiewicz-Banecka, J., Piotrowska, E. és mtsai: Gene expression-targeted isoflavone therapy (GET IT) for mucopolysaccharidosis type III (Sanfilippo disease): a pilot clinical trial. J. Inherit. Metabol. Dis., 2007, 30 (Suppl. 1) , 116.

    Piotrowska E. , 'Gene expression-targeted isoflavone therapy (GET IT) for mucopolysaccharidosis type III (Sanfilippo disease): a pilot clinical trial ' (2007 ) 30 J. Inherit. Metabol. Dis. : 116 -.

    • Search Google Scholar
  • Hobbs, J. R., Hugh-Jonwa, K., Barrett, A. J. és mtsai: Reversal of clinical features of Hurler’s disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet, 1981, 2 , 709–712.

    Barrett A. J. , 'Reversal of clinical features of Hurler’s disease and biochemical improvement after treatment by bone-marrow transplantation ' (1981 ) 2 Lancet : 709 -712.

    • Search Google Scholar
  • Peters, C., Shapiro, E. G., Krivit, W.: Neuropsychological development in children with Hurler syndrome following hematopoietic stem cell transplantation. Pediatr. Transplant., 1998, 2 , 250–253.

    Krivit W. , 'Neuropsychological development in children with Hurler syndrome following hematopoietic stem cell transplantation ' (1998 ) 2 Pediatr. Transplant. : 250 -253.

    • Search Google Scholar
  • Orchard, P. J., Bruce, R., Wagner, J. és mtsai: Hematopoetic cell therapy for metabolic disease. J. Pediatr., 2007, 151 , 304–306.

    Wagner J. , 'Hematopoetic cell therapy for metabolic disease ' (2007 ) 151 J. Pediatr. : 304 -306.

    • Search Google Scholar
  • Staba, S. L., Escolar, M. L., Poe, M. és mtsai: Cord-blood transplants from unrelated donor sin patients with Hurler’ syndrome. N. Eng. J. Med., 2004, 350 , 1960–1969.

    Poe M. , 'Cord-blood transplants from unrelated donor sin patients with Hurler’ syndrome ' (2004 ) 350 N. Eng. J. Med. : 1960 -1969.

    • Search Google Scholar
  • Krivit, W.: Allogenic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin. Immunopathol., 2004, 24 , 119–132.

    Krivit W. , 'Allogenic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases ' (2004 ) 24 Springer Semin. Immunopathol. : 119 -132.

    • Search Google Scholar
  • Ellinwood, N. M., Vite, C. H., Haskins, M. E.: Gene therapy for lysosomal storage disease: the lessons and promise of animal models. J. Gene Med., 2004, 6 , 481–506.

    Haskins M. E. , 'Gene therapy for lysosomal storage disease: the lessons and promise of animal models ' (2004 ) 6 J. Gene Med. : 481 -506.

    • Search Google Scholar
  • Anson, D. S.: The use of retroviral vectors for gene therapy – what are the risks? A review of retroviral pathogenesis and its relevance to retroviral vector-mediated gene delivery. Genet. Vaccines Ther., 2004, 2 , 9–22.

    Anson D. S. , 'The use of retroviral vectors for gene therapy – what are the risks? A review of retroviral pathogenesis and its relevance to retroviral vector-mediated gene delivery ' (2004 ) 2 Genet. Vaccines Ther. : 9 -22.

    • Search Google Scholar