1932

Abstract

Lysosomal storage diseases are a group of rare, inborn, metabolic errors characterized by deficiencies in normal lysosomal function and by intralysosomal accumulation of undegraded substrates. The past 25 years have been characterized by remarkable progress in the treatment of these diseases and by the development of multiple therapeutic approaches. These approaches include strategies aimed at increasing the residual activity of a missing enzyme (enzyme replacement therapy, hematopoietic stem cell transplantation, pharmacological chaperone therapy and gene therapy) and approaches based on reducing the flux of substrates to lysosomes. As knowledge has improved about the pathophysiology of lysosomal storage diseases, novel targets for therapy have been identified, and innovative treatment approaches are being developed.

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2015-01-14
2024-03-28
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Literature Cited

  1. Braulke T, Bonifacino JS. 1.  2009. Sorting of lysosomal proteins. Biochim. Biophys. Acta 1793:605–14 [Google Scholar]
  2. Reczek D, Schwake M, Schroder J. 2.  et al. 2007. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of β-glucocerebrosidase. Cell 131:770–83 [Google Scholar]
  3. Lieberman AP, Puertollano R, Raben N. 3.  et al. 2012. Autophagy in lysosomal storage disorders. Autophagy 8:719–30 [Google Scholar]
  4. Sancak Y, Bar-Peled L, Zoncu R. 4.  et al. 2010. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141:290–303 [Google Scholar]
  5. Zoncu R, Bar-Peled L, Efeyan A. 5.  et al. 2011. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H+-ATPase. Science 334:678–83 [Google Scholar]
  6. Sardiello M, Palmieri M, di Ronza A. 6.  et al. 2009. A gene network regulating lysosomal biogenesis and function. Science 325:473–77 [Google Scholar]
  7. Settembre C, Zoncu R, Medina DL. 7.  et al. 2012. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 31:1095–108 [Google Scholar]
  8. Fuller M, Meikle PJ, Hopwood JJ. 8.  2006. Epidemiology of lysosomal storage diseases: an overview. Fabry Disease: Perspectives from 5 Years of FOS A Mehta, M Beck, G Sunder-Plassmann Oxford: Oxford PharmaGenesis http://www.ncbi.nlm.nih.gov/pubmed/21290699 [Google Scholar]
  9. Nascimbeni AC, Fanin M, Masiero E. 9.  et al. 2012. The role of autophagy in the pathogenesis of glycogen storage disease type II (GSDII). Cell Death Differ. 19:1698–708 [Google Scholar]
  10. Shea L, Raben N. 10.  2009. Autophagy in skeletal muscle: implications for Pompe disease. Int. J. Clin. Pharmacol. Ther. 47:Suppl. 1S42–47 [Google Scholar]
  11. Settembre C, Fraldi A, Jahreiss L. 11.  et al. 2008. A block of autophagy in lysosomal storage disorders. Hum. Mol. Genet. 17:119–29 [Google Scholar]
  12. Lloyd-Evans E, Morgan AJ, He X. 12.  et al. 2008. Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium. Nat. Med. 14:1247–55 [Google Scholar]
  13. Fraldi A, Annunziata F, Lombardi A. 13.  et al. 2010. Lysosomal fusion and SNARE function are impaired by cholesterol accumulation in lysosomal storage disorders. EMBO J. 29:3607–20 [Google Scholar]
  14. Neudorfer O, Giladi N, Elstein D. 14.  et al. 1996. Occurrence of Parkinson's syndrome in type I Gaucher disease. QJM 89:691–94 [Google Scholar]
  15. Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. 15.  2004. Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N. Engl. J. Med. 351:1972–77 [Google Scholar]
  16. Dehay B, Martinez-Vicente M, Caldwell GA. 16.  et al. 2013. Lysosomal impairment in Parkinson's disease. Mov. Disord. 28:725–32 [Google Scholar]
  17. Dehay B, Martinez-Vicente M, Ramirez A. 17.  et al. 2012. Lysosomal dysfunction in Parkinson disease: ATP13A2 gets into the groove. Autophagy 8:1389–91 [Google Scholar]
  18. Settembre C, Fraldi A, Medina DL, Ballabio A. 18.  2013. Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat. Rev. Mol. Cell Biol. 14:283–96 [Google Scholar]
  19. Sly WS, Fischer HD. 19.  1982. The phosphomannosyl recognition system for intracellular and intercellular transport of lysosomal enzymes. J. Cell. Biochem. 18:67–85 [Google Scholar]
  20. Barton NW, Brady RO, Dambrosia JM. 20.  et al. 1991. Replacement therapy for inherited enzyme deficiency–macrophage-targeted glucocerebrosidase for Gaucher's disease. N. Engl. J. Med. 324:1464–70 [Google Scholar]
  21. Barton NW, Furbish FS, Murray GJ. 21.  et al. 1990. Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc. Natl. Acad. Sci. USA 87:1913–16 [Google Scholar]
  22. Eng CM, Guffon N, Wilcox WR. 22.  et al. 2001. Safety and efficacy of recombinant human α-galactosidase A replacement therapy in Fabry's disease. N. Engl. J. Med. 345:9–16 [Google Scholar]
  23. Schiffmann R, Kopp JB, Austin HA 3rd. 23.  et al. 2001. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 285:2743–49 [Google Scholar]
  24. Van den Hout H, Reuser AJ, Vulto AG. 24.  et al. 2000. Recombinant human α-glucosidase from rabbit milk in Pompe patients. Lancet 356:397–98 [Google Scholar]
  25. Kakkis ED, Muenzer J, Tiller GE. 25.  et al. 2001. Enzyme-replacement therapy in mucopolysaccharidosis I. N. Engl. J. Med. 344:182–88 [Google Scholar]
  26. Muenzer J, Wraith JE, Beck M. 26.  et al. 2006. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet. Med. 8:465–73 [Google Scholar]
  27. Harmatz P, Giugliani R, Schwartz I. 27.  et al. 2006. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J. Pediatr. 148:533–39 [Google Scholar]
  28. Brady RO.28.  2006. Enzyme replacement for lysosomal diseases. Annu. Rev. Med. 57:283–96 [Google Scholar]
  29. Lachmann RH.29.  2011. Enzyme replacement therapy for lysosomal storage diseases. Curr. Opin. Pediatr. 23:588–93 [Google Scholar]
  30. Wraith JE.30.  2006. Limitations of enzyme replacement therapy: current and future. J. Inherit. Metab. Dis. 29:442–47 [Google Scholar]
  31. Parenti G, Andria G. 31.  2011. Pompe disease: from new views on pathophysiology to innovative therapeutic strategies. Curr. Pharm. Biotechnol. 12:902–15 [Google Scholar]
  32. Prater SN, Banugaria SG, DeArmey SM. 32.  et al. 2012. The emerging phenotype of long-term survivors with infantile Pompe disease. Genet. Med. 14:800–10 [Google Scholar]
  33. Wyatt K, Henley W, Anderson L. 33.  et al. 2012. The effectiveness and cost-effectiveness of enzyme and substrate replacement therapies: a longitudinal cohort study of people with lysosomal storage disorders. Health Technol. Assess. 16:391–543 [Google Scholar]
  34. Anson DS, McIntyre C, Byers S. 34.  2011. Therapies for neurological disease in the mucopolysaccharidoses. Curr. Gene Ther. 11:132–43 [Google Scholar]
  35. Begley DJ, Pontikis CC, Scarpa M. 35.  2008. Lysosomal storage diseases and the blood-brain barrier. Curr. Pharm. Des. 14:1566–80 [Google Scholar]
  36. Grubb JH, Vogler C, Levy B. 36.  et al. 2008. Chemically modified β-glucuronidase crosses blood-brain barrier and clears neuronal storage in murine mucopolysaccharidosis VII. Proc. Natl. Acad. Sci. USA 105:2616–21 [Google Scholar]
  37. Huynh HT, Grubb JH, Vogler C, Sly WS. 37.  2012. Biochemical evidence for superior correction of neuronal storage by chemically modified enzyme in murine mucopolysaccharidosis VII. Proc. Natl. Acad. Sci. USA 109:17022–27 [Google Scholar]
  38. Boado RJ, Zhang Y, Zhang Y. 38.  et al. 2008. Genetic engineering, expression, and activity of a chimeric monoclonal antibody-avidin fusion protein for receptor-mediated delivery of biotinylated drugs in humans. Bioconjug. Chem. 19:731–39 [Google Scholar]
  39. Osborn MJ, McElmurry RT, Peacock B. 39.  et al. 2008. Targeting of the CNS in MPS-IH using a nonviral transferrin-α-l-iduronidase fusion gene product. Mol. Ther. 16:1459–66 [Google Scholar]
  40. Zhou QH, Boado RJ, Lu JZ. 40.  et al. 2012. Brain-penetrating IgG-iduronate 2-sulfatase fusion protein for the mouse. Drug Metab. Dispos. 40:329–35 [Google Scholar]
  41. Bockenhoff A, Cramer S, Wolte P. 41.  et al. 2014. Comparison of five peptide vectors for improved brain delivery of the lysosomal enzyme arylsulfatase A. J. Neurosci. 34:3122–29 [Google Scholar]
  42. Meng Y, Sohar I, Sleat DE. 42.  et al. 2014. Effective intravenous therapy for neurodegenerative disease with a therapeutic enzyme and a peptide that mediates delivery to the brain. Mol. Ther. 22:547–53 [Google Scholar]
  43. Sorrentino NC, D'Orsi L, Sambri I. 43.  et al. 2013. A highly secreted sulphamidase engineered to cross the blood-brain barrier corrects brain lesions of mice with mucopolysaccharidoses type IIIA. EMBO Mol. Med. 5:675–90 [Google Scholar]
  44. Kakkis E, McEntee M, Vogler C. 44.  et al. 2004. Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I. Mol. Genet. Metab. 83:163–74 [Google Scholar]
  45. Dickson P, McEntee M, Vogler C. 45.  et al. 2007. Intrathecal enzyme replacement therapy: successful treatment of brain disease via the cerebrospinal fluid. Mol. Genet. Metab. 91:61–68 [Google Scholar]
  46. Auclair D, Finnie J, White J. 46.  et al. 2010. Repeated intrathecal injections of recombinant human 4-sulphatase remove dural storage in mature mucopolysaccharidosis VI cats primed with a short-course tolerisation regimen. Mol. Genet. Metab. 99:132–41 [Google Scholar]
  47. Auclair D, Finnie J, Walkley SU. 47.  et al. 2012. Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats. Pediatr. Res. 71:39–45 [Google Scholar]
  48. Munoz-Rojas MV, Vieira T, Costa R. 48.  et al. 2008. Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression. Am. J. Med. Genet. A 146A:2538–44 [Google Scholar]
  49. Zhu Y, Li X, Kyazike J. 49.  et al. 2004. Conjugation of mannose 6-phosphate-containing oligosaccharides to acid α-glucosidase improves the clearance of glycogen in Pompe mice. J. Biol. Chem. 279:50336–41 [Google Scholar]
  50. Tiels P, Baranova E, Piens K. 50.  et al. 2012. A bacterial glycosidase enables mannose-6-phosphate modification and improved cellular uptake of yeast-produced recombinant human lysosomal enzymes. Nat. Biotechnol. 30:1225–31 [Google Scholar]
  51. Zhou Q, Stefano JE, Harrahy J. 51.  et al. 2011. Strategies for Neoglycan conjugation to human acid α-glucosidase. Bioconjug. Chem. 22:741–51 [Google Scholar]
  52. Maga JA, Zhou J, Kambampati R. 52.  et al. 2013. Glycosylation-independent lysosomal targeting of acid α-glucosidase enhances muscle glycogen clearance in Pompe mice. J. Biol. Chem. 288:1428–38 [Google Scholar]
  53. Hsu J, Northrup L, Bhowmick T, Muro S. 53.  2012. Enhanced delivery of α-glucosidase for Pompe disease by ICAM-1-targeted nanocarriers: comparative performance of a strategy for three distinct lysosomal storage disorders. Nanomedicine 8:731–39 [Google Scholar]
  54. Hsu J, Bhowmick T, Burks SR. 54.  et al. 2014. Enhancing biodistribution of therapeutic enzymes in vivo by modulating surface coating and concentration of ICAM-1-targeted nanocarriers. J. Biomed. Nanotechnol. 10:345–54 [Google Scholar]
  55. Koeberl DD, Austin S, Case LE. 55.  et al. 2014. Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease. FASEB J. 28:2171–76 [Google Scholar]
  56. Farah BL, Madden L, Li S. 56.  et al. 2014. Adjunctive β2-agonist treatment reduces glycogen independently of receptor-mediated acid α-glucosidase uptake in the limb muscles of mice with Pompe disease. FASEB J. 28:2272–80 [Google Scholar]
  57. Ponder KP.57.  2008. Immune response hinders therapy for lysosomal storage diseases. J. Clin. Investig. 118:2686–89 [Google Scholar]
  58. Banugaria SG, Prater SN, Patel TT. 58.  et al. 2013. Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile Pompe disease: a step towards improving the efficacy of ERT. PLOS ONE 8e67052
  59. Banugaria SG, Prater SN, McGann JK. 59.  et al. 2013. Bortezomib in the rapid reduction of high sustained antibody titers in disorders treated with therapeutic protein: lessons learned from Pompe disease. Genet. Med. 15:123–31 [Google Scholar]
  60. Zimran A, Brill-Almon E, Chertkoff R. 60.  et al. 2011. Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood 118:5767–73 [Google Scholar]
  61. Reggi S, Marchetti S, Patti T. 61.  et al. 2005. Recombinant human acid β-glucosidase stored in tobacco seed is stable, active and taken up by human fibroblasts. Plant Mol. Biol. 57:101–13 [Google Scholar]
  62. Martiniuk F, Reggi S, Tchou-Wong KM. 62.  et al. 2013. Production of a functional human acid maltase in tobacco seeds: biochemical analysis, uptake by human GSDII cells, and in vivo studies in GAA knockout mice. Appl. Biochem. Biotechnol. 171:916–26 [Google Scholar]
  63. Patti T, Bembi B, Cristin P. 63.  et al. 2012. Endosperm-specific expression of human acid beta-glucosidase in a waxy rice. Rice 5:34 [Google Scholar]
  64. Orchard PJ, Blazar BR, Wagner J. 64.  et al. 2007. Hematopoietic cell therapy for metabolic disease. J. Pediatr. 151:340–46 [Google Scholar]
  65. Boelens JJ, Prasad VK, Tolar J. 65.  et al. 2010. Current international perspectives on hematopoietic stem cell transplantation for inherited metabolic disorders. Pediatr. Clin. North Am. 57:123–45 [Google Scholar]
  66. Parenti G, Fecarotta S, Moracci M, Andria G. 66.  2014. Pharmacological chaperone therapy for lysosomal storage diseases. Future Med. Chem. 6:1031–45 [Google Scholar]
  67. Parenti G.67.  2009. Treating lysosomal storage diseases with pharmacological chaperones: from concept to clinics. EMBO Mol. Med. 1:268–79 [Google Scholar]
  68. Valenzano KJ, Khanna R, Powe AC. 68.  et al. 2011. Identification and characterization of pharmacological chaperones to correct enzyme deficiencies in lysosomal storage disorders. Assay Drug Dev. Technol. 9:213–35 [Google Scholar]
  69. Shen JS, Edwards NJ, Hong YB, Murray GJ. 69.  2008. Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase. Biochem. Biophys. Res. Commun. 369:1071–75 [Google Scholar]
  70. Porto C, Cardone M, Fontana F. 70.  et al. 2009. The pharmacological chaperone N-butyldeoxynojirimycin enhances enzyme replacement therapy in Pompe disease fibroblasts. Mol. Ther. 17:964–71 [Google Scholar]
  71. Porto C, Pisani A, Rosa M. 71.  et al. 2012. Synergy between the pharmacological chaperone 1-deoxygalactonojirimycin and the human recombinant alpha-galactosidase A in cultured fibroblasts from patients with Fabry disease. J. Inherit. Metab. Dis. 35:513–20 [Google Scholar]
  72. Benjamin ER, Khanna R, Schilling A. 72.  et al. 2012. Co-administration with the pharmacological chaperone AT1001 increases recombinant human α-galactosidase A tissue uptake and improves substrate reduction in Fabry mice. Mol. Ther. 20:717–26 [Google Scholar]
  73. Khanna R, Flanagan JJ, Feng J. 73.  et al. 2012. The pharmacological chaperone AT2220 increases recombinant human acid α-glucosidase uptake and glycogen reduction in a mouse model of Pompe disease. PLOS ONE 7:e40776 [Google Scholar]
  74. Parenti G, Fecarotta S, la Marca G. 74.  et al. 2014. A chaperone enhances blood α-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy. Mol. Ther. 222004–12
  75. Mu TW, Ong DS, Wang YJ. 75.  et al. 2008. Chemical and biological approaches synergize to ameliorate protein-folding diseases. Cell 134:769–81 [Google Scholar]
  76. Song W, Wang F, Savini M. 76.  et al. 2013. TFEB regulates lysosomal proteostasis. Hum. Mol. Genet. 22:1994–2009 [Google Scholar]
  77. Ong DS, Wang YJ, Tan YL. 77.  2013. FKBP10 depletion enhances glucocerebrosidase proteostasis in Gaucher disease fibroblasts. Chem. Biol. 20:403–15 [Google Scholar]
  78. Platt FM, Jeyakumar M. 78.  2008. Substrate reduction therapy. Acta Paediatr. 97:Suppl.88–93 [Google Scholar]
  79. Schiffmann R.79.  2010. Agalsidase treatment for Fabry disease: uses and rivalries. Genet. Med. 12:684–85 [Google Scholar]
  80. Cox T, Lachmann R, Hollak C. 80.  et al. 2000. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 355:1481–85 [Google Scholar]
  81. Patterson MC, Vecchio D, Prady H. 81.  et al. 2007. Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol. 6:765–72 [Google Scholar]
  82. Lukina E, Watman N, Arreguin EA. 82.  et al. 2010. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood 116:4095–98 [Google Scholar]
  83. Piotrowska E, Jakobkiewicz-Banecka J, Tylki-Szymanska A. 83.  et al. 2008. Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: an open-label, pilot study in 10 pediatric patients. Curr. Ther. Res. Clin. Exp. 69:166–79 [Google Scholar]
  84. Sands MS, Davidson BL. 84.  2006. Gene therapy for lysosomal storage diseases. Mol. Ther. 13:839–49 [Google Scholar]
  85. Biffi A, Montini E, Lorioli L. 85.  et al. 2013. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341:1233158 [Google Scholar]
  86. Raben N, Schreiner C, Baum R. 86.  et al. 2010. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder—murine Pompe disease. Autophagy 6:1078–89 [Google Scholar]
  87. Medina DL, Fraldi A, Bouche V. 87.  et al. 2011. Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev. Cell 21:421–30 [Google Scholar]
  88. Spampanato C, Feeney E, Li L. 88.  et al. 2013. Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease. EMBO Mol. Med. 5:691–706 [Google Scholar]
  89. Williams IM, Wallom KL, Smith DA. 89.  et al. 2014. Improved neuroprotection using miglustat, curcumin and ibuprofen as a triple combination therapy in Niemann-Pick disease type C1 mice. Neurobiol. Dis. 67:9–17 [Google Scholar]
  90. Kirkegaard T, Roth AG, Petersen NH. 90.  et al. 2010. Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature 463:549–53 [Google Scholar]
  91. Petersen NH, Kirkegaard T. 91.  2010. HSP70 and lysosomal storage disorders: novel therapeutic opportunities.. Biochem. Soc. Trans. 38:1479–83 [Google Scholar]
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