Recent developments in therapeutic approaches for lysosomal storage diseases

Recent Patents on CNS Drug Discovery

Volumn 6, Issue 1, 2011, Pages 1-19

  Urbanelli, Lorena ^a   Magini, Alessandro ^a   Polchi, Alice ^a   Polidoro, Mario ^a   Emiliani, Carla ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

Author keywords

Enzyme biodistribution; Enzyme delivery; Enzyme replacement therapy; Enzyme targeting; Gene therapy; Lysosomal storage disorders; Lysosomes; Mannose 6 phosphate receptors; Metabolic cross correction; Pharmacological chaperone therapy; Protein glycosylation; Protein phosphorylation; Proteostasis; Stem cells; Substrate reduction therapy

Indexed keywords

AGALSIDASE ALFA; AGALSIDASE BETA; ALGLUCERASE; ALPHA MANNOSIDASE; BETA GLUCOSIDASE; GALSULFASE; IDURONATE 2 SULFATASE; IMIGLUCERASE; LARONIDASE; RECOMBINANT ENZYME; RECOMBINANT GLUCAN 1,4 ALPHA GLUCOSIDASE; TALIGLUCERASE ALFA; VELAGLUCERASE ALFA;

ADENO ASSOCIATED VIRUS; CELL BASED GENE THERAPY; ENZYME PHOSPHORYLATION; ENZYME REPLACEMENT; FABRY DISEASE; GAUCHER DISEASE; GENE THERAPY; GLYCOGEN STORAGE DISEASE TYPE 2; HUMAN; LYSOSOME STORAGE DISEASE; MANNOSIDOSIS; MOLECULAR BIOLOGY; NIEMANN PICK DISEASE; NONHUMAN; PATENT; PRIORITY JOURNAL; PROTEIN GLYCOSYLATION; REVIEW; VIRAL GENE THERAPY;

ENZYME REPLACEMENT THERAPY; GENE THERAPY; GENETIC VECTORS; HUMANS; HYDROLASES; LYSOSOMAL STORAGE DISEASES; LYSOSOMES; MENTAL RETARDATION; MOLECULAR CHAPERONES; STEM CELL TRANSPLANTATION;

EID: 78650962383     PISSN: 15748898     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488911794079127     Document Type: Review

References (163)

1. Wraith JE. Lysosomal disorders. Semin Neonatol 2002; 7: 75-83.
2. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence oflysosomal storage disorders. JAMA 1999; 281: 249-54.
3. Futerman AH, van Meer G. The cell biology of lysosomal storagedisorders. Nat Rev Mol Cell Biol 2004; 5: 554-65.
4. Ballabio A, Gieselmann V. Lysosomal disorders: From storage tocellular damage. Biochim Biophys Acta 2009; 1793: 684-96.
5. Settembre C, Fraldi A, Jahreiss L, Spampanato C, Venturi C, Medina D, et al. A block of autophagy in lysosomal storage disorders. Hum Mol Genet 2008; 17: 119-29.
6. Bahr BA, Bendiske J. The neuropathogenic contributions oflysosomal dysfunction. J Neurochem 2002; 83: 481-9.
7. Ballabio A. Disease pathogenesis explained by basic science:Lysosomal storage diseases as autophagocytic disorders. Int J ClinPharmacol Ther 2009; 47(Suppl 1): S34-8.
8. Winchester B, Vellodi A, Young E. The molecular basis of lysosomal storage diseases and their treatment. Biochem Soc Trans 2000; 28: 150-4.
9. Saftig P, Klumperman J. Lysosome biogenesis and lysosomalmembrane proteins: Trafficking meets function. Nat Rev Mol Cell Biol 2009; 10: 623-35.
10. Braulke T, Bonifacino JS. Sorting of lysosomal proteins. BiochimBiophys Acta 2009; 1793: 605-14.
11. Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X, et al.LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell 2007; 131:770-83.
12. Zeng J, Racicott J, Morales CR. The inactivation of the sortilingene leads to a partial disruption of prosaposin trafficking to the lysosomes. Exp Cell Res 2009; 315: 3112-4.
13. Ghosh P, Dahms NM, Kornfeld S. Mannose 6-phosphate receptors:New twists in the tale. Nat Rev Mol Cell Biol 2003; 4: 202-12.
14. Jeyakumar M, Dwek RA, Butters TD, Platt FM. Storage solutions:Treating lysosomal disorders of the brain. Nat Rev Neurosci 2005; 6: 713-25.
15. Platt FM, Jeyakumar M, Andersson U, Priestman DA, Dwek RA, Butters TD, et al. Inhibition of substrate synthesis as a strategy forglycolipid lysosomal storage disease therapy. J Inherit Metab Dis2001; 24: 275-90.
16. Beck M. New therapeutic options for lysosomal storage disorders:enzyme replacement, small molecules and gene therapy. HumGenet 2007; 121: 1-22.
17. Platt FM, Lachmann RH. Treating lysosomal storage disorders:Current practice and future prospects. Biochim Biophys Acta 2009; 1793: 737-45.
18. Parenti G. Treating lysosomal storage diseases withpharmacological chaperones: From concept to clinics. EMBO MolMed 2009; 1: 268-79.
19. Beck M. Therapy for lysosomal storage disorders. IUBMB Life2010; 62: 33-40.
20. Beck M. Emerging drugs for lysosomal storage diseases. Expert Opin Emerg Drugs 2010; 15: 495-507.
21. Brady RO. Enzyme replacement for lysosomal diseases. Annu RevMed 2006; 57: 283-96.
22. Rohrbach M, Clarke JT. Treatment of lysosomal storage disorders:Progress with enzyme replacement therapy. Drugs 2007; 67: 2697-716.
23. Barton NW, Furbish FS, Murray GJ, Garfield M, Brady RO. Therapeutic response to intravenous infusions of glucocerebro-sidase in a patient with Gaucher disease. Proc Natl Acad Sci USA 1990; 87: 1913-6.
24. Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC, et al. Replacement therapy for inherited enzymedeficiency-macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med 1991; 324: 1464-70.
25. Grabowski GA, Barton NW, Pastores G, Dambrosia JM, Banerjee TK, McKee M. A, et al. Enzyme therapy in type 1 Gaucher disease:Comparative efficacy of mannose-terminated glucocerebrosidasefrom natural and recombinant sources. Ann Intern Med 1995; 122:33-9.
26. Wraith JE. Limitations of enzyme replacement therapy: Current and future. J Inherit Metab Dis 2006; 29: 442-7.
27. Wraith JE. Enzyme replacement therapy for the management of the mucopolysaccharidoses. Int J Clin Pharmacol Ther 2009; 47(Suppl1): S63-5.
28. Schiffmann R, Kopp JB, Austin HA, 3rd, Sabnis S, Moore D. F, Weibel T, et al. Enzyme replacement therapy in Fabry disease: Arandomized controlled trial. JAMA 2001; 285: 2743-9.
29. Fukuda T, Ewan L, Bauer M, Mattaliano RJ, Zaal K, Ralston E, et al. Dysfunction of endocytic and autophagic pathways in alysosomal storage disease. Ann Neurol 2006; 59: 700-8.
30. Cardone M, Porto C, Tarallo A, Vicinanza M, Rossi B, Polishchuk, E, et al. Abnormal mannose-6-phosphate receptor traffickingimpairs recombinant alpha-glucosidase uptake in Pompe diseasefibroblasts. Pathogenetics 2008; 1: 6.
31. Koeberl DD, Kishnani PS. Immuno modulatory gene therapy inlysosomal storage disorders. Curr Gene Ther 2009; 9: 503-10.
32. Beutler E. Lysosomal storage diseases: Natural history and ethicaland economic aspects. Mol Genet Metab 2006; 88: 208-15.
33. Van Patten, S.M., Karey, K.P., Qiu, H. Modified human acidsphingomyelinase having increased activity, and methods for making the same. WO2004111198 (2004).
34. Andersson, C., Fogh, J., Weigelt, C., Roces, D.P., Von Figura, K., Irani, M. Medical use of alpha-mannosidase. WO2005094874 (2005).
35. Canfield, W.M., Kudo, M. Soluble GLcNAC phosphotransferase.WO2003057826 (2003).
36. Canfield, W.M., Kornfeld, S. Expression of lysosomal hydrolase incells expressing pro-n-acetylglucosamine-1-phosphodiester alpha-n-acetyl glucosimanidase. WO2003057138 (2003).
37. Canfield, W.M. Methods of producing high mannose glycoproteinsin complex carbohydrate deficient cells. WO2003057710 (2003).
38. Canfield, W.M. Highly phosphorylated acid beta-glucocere-brosidase and methods of treating Gaucher's disease.WO2003056897 (2003).
39. Okkels, J.S., Jensen, A.D., Halkier, T., Jensen, R.B., Schambye, H.T. Improved lysosomal enzymes and lysosomal enzymeactivators. WO2001049830 (2001).
40. Aertsm J.M.F.G. Compositions and methods for improving enzymereplacement therapy of lysosomal storage diseases.WO2003068255 (2003).
41. Zhu, Y., Cheng, S.H. Methods of enhancing lysosomal storage disease therapy. WO2003086452 (2003).
42. Zankel, T., Kakkis, E.D. Manufacture of highly phosphorylatedlysosomal enzymes and uses thereof. WO2005077093 (2005).
43. Zankel, T., Zecherle, G.N., Starr, C.M., Christiansson, T. M. Methods of activation of sulfatases and methods and compositionsof using the same. WO2005113765 (2005).
44. Slym W.S., Vogler, C.A., Grubb, J.H. Modified enzyme andtreatment method. WO2008109677 (2008).
45. Lee, K.L., Mattaliano, R.J., Stefano, J.E. Oligosaccharideconjugates for cellular targeting. WO2008089339 (2008).
46. Vellard, M.C., Koppaka, V., Dvorak-Ewell, M., Pungor, E., Hague, C.:, Charles E. Manufacture of active highly phosphorylated humanlysosomal sulfatase enzymes and uses thereof. WO2009091994 (2009).
47. Zhu Y, Jiang JL, Gumlaw NK, Zhang J, Bercury SD, Ziegler RJ, et al. Glycoengineered acid alpha-glucosidase with improvedefficacy at correcting the metabolic aberrations and motor functiondeficits in a mouse model of Pompe disease. Mol Ther 2009; 17:954-63.
48. Brooks SA. Appropriate glycosylation of recombinant proteins forhuman use: Implications of choice of expression system. Mol Biotechnol 2004; 28: 241-55.
49. Li H, d'Anjou M. Pharmacological significance of glycosylation intherapeutic proteins. Curr Opin Biotechnol 2009; 20: 678-84.
50. Grubb JH, Vogler C, Levy B, Galvin N, Tan Y, Sly W. S. Chemically modified beta-glucuronidase crosses blood-brain barrierand clears neuronal storage in murine mucopoly-saccharidosis VII.Proc Natl Acad Sci USA 2008; 105: 2616-21.
51. Harmatz P, Giugliani R, Schwartz I, Guffon N, Teles EL, Miranda, M. C., et al. Enzyme replacement therapy for mucopolysaccharidosisVI: A phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr 2006; 148: 533-9.
52. Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz T J., Kimura A. A phase I/II clinical trial of enzyme replacementtherapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab 2007; 90: 329-37.
53. Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores G. M., Muenzer J, et al. Enzyme replacement therapy for muco-polysaccharidosis I: A randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr 2004; 144: 581-8.
54. Gieselmann V. Reversibility of cellular and organ pathology inenzyme replacement trials in animal models of lysosomal storagediseases. Acta Paediatr Suppl 2006; 95: 93-9.
55. Stefano, J. PEG and polysialic lysosomal enzyme conjugates viaacid labile linkers for therapeutic targeting. WO2006108052(2006).
56. Galindo, S.M., Muzykantov, V.R., Schuchman, E.H. Targetedprotein replacement for the treatment of lysosomal storagedisorders. WO2006007560 (2006).
57. Arranz, V. Compositions and methods for treating lysosomalstorage diseases. WO2007091159 (2007).
58. Stern, N., Navon, R., Futerman, A., Zimran, A., Oscher, E. Enzymereplacement therapy for treating lysosomal storage diseases.WO2007091250 (2007).
59. Reczek, D.J., Saftig, P., Demaria, C.T. Methods of producing asecreted protein. WO2008143797 (2008).
60. Lebowitz, J., Maga, J. Lysosomal targeting peptides and uses thereof. WO2009137721 (2009).
61. Sturk, L.M., Lamsa, J.C., Heartlein, M.W., Nguyen, V., Taylor, K. D., Shahrokh, Z. Subcutaneous administration of alpha-galatosidase A. WO2009032171 (2009).
62. Kakkis, E.D. Delivery of therapeutic compounds to the brain andother tissues. WO2005021064 (2005).
63. Dodge, J., Passini, M., Shihabuddin, L., Cheng, S. Intraventricularenzyme delivery for lysosomal storage diseases. WO2007084737(2007).
64. Shih SM, Doran PM. Foreign protein production using plant celland organ cultures: Advantages and limitations. Biotechnol Adv2009; 27: 1036-42.
65. Garger, S.J., Turpen, T.H., Kumagai, M.H. Production of lysoso-mal enzymes in plants by transient expression. WO2002008404(2002).
66. Fogher, C., Reggi, S. Expression of lysosomal enzymes in plantseeds. WO2003073839 (2003).
67. Shaaltiel, Y., Baum, G., Bartfeld, D., Hashmueli, S., Lewkowicz, A. Production of high mannose proteins in plant culture.WO2008132743 (2008).
68. Raben, N., Lu, N., Plotz, P., Rivera, Y. Synthesis and secretion ofrecombinant lysosomal enzymes by liver. WO2002081648 (2002).
69. D'Azzo, A., Bonten, E. Targeting proteins to cells expressingmannose receptors via expression in insect cells. WO2003029403 (2003).
70. Hartmann, M, Weide, T., Bockau, U. Recombinant lysosomalenzymes comprising a glycosylation pattern typical of ciliates for treatment. WO2005099748 (2005).
71. Marchetti, S., Bembi, B., Patti, T., Cristin, P. A method for theproduction of a human protein in a plant, in particular a humanrecombinant lysosomal enzyme in a cereal endosperm.WO2009112508 (2009).
72. Heilbronn R, Weger S. Viral vectors for gene transfer: Currentstatus of gene therapeutics. Handb Exp Pharmacol 2010; (197):143-70.
73. Sands MS, Davidson BL. Gene therapy for lysosomal storagediseases. Mol Ther 2006; 13: 839-49.
74. Cardone M. Prospects for gene therapy in inherited neuro-degenerative diseases. Curr Opin Neurol 2007; 20: 151-8.
75. Biffi A, Naldini L. Gene therapy of storage disorders by retroviraland lentiviral vectors. Hum Gene Ther 2005; 16: 1133-42.
76. Warrington KH, Jr., Herzog RW. Treatment of human disease byadeno-associated viral gene transfer. Hum Genet 2006; 119: 571-603.
77. Ponder KP, Haskins ME. Gene therapy for mucopolysaccharidosis.Expert Opin Biol Ther 2007; 7: 1333-45.
78. Connolly JB. Lentiviruses in gene therapy clinical research. Gene Ther 2002; 9: 1730-4.
79. Lundberg C, Bjorklund T, Carlsson T, Jakobsson J, Hantraye P, Deglon N, et al. Applications of lentiviral vectors for biology andgene therapy of neurological disorders. Curr Gene Ther 2008; 8:461-73.
80. Desmaris, N., Heard, J.M. Vector for expressing -L-iduronidaseand method of treating MPS I by stereotactic injection into the brain of a mammal. US7090836 (2002).
81. Desmaris, N., Heard, J.M. Vector for expressing alpha-N-acetyl-galactosaminidase and method of treating MPS I by stereotacticinjection into the brain of a mammal. US20060182717 (2006).
82. Yew, N.S., Ziegler, R.J., Cheng, S. Compositions and methods fortreating lysosomal storage disease. WO2000009153 (2000).
83. Podsakoff, G., Watson, G., Couto, L. B., Yang, B. Recombinantadeno-associated virus virions for the treatment of lysosomaldisorders. WO2001036603 (2001).
84. Whitley, C.B., McIvor, S.R. Methods of using vectors to treatmetabolic disorders. WO2004055157 (2004).
85. Passini, M., Dodge, J., Stewart, G.R. Gene therapy forneurometabolic disorders. WO2006119458 (2006).
86. Passini, M., Ziegler, R.J., Dodge, J., Shihabuddin, L., Cheng, S.H. Gene therapy for niemann-pick disease type A. WO2007092563 (2007).
87. Dodge, J., Cheng, S.H. Gene therapy for lysosomal storagediseases. WO2008154198 (2008).
88. Barkats, M. CNS gene delivery using peripheral administration of AAV vectors. WO2009013290 (2009).
89. Terzi D, Zachariou V. Adeno-associated virus-mediated genedelivery approaches for the treatment of CNS disorders. Bio technol J 2008; 3: 1555-63.
90. Davidson, B.L., Jolly, D.J., Sauter, S.L., Ghodsi, A., Stein, C.S., Derksen, T.A., Dubensky, T.W. Use of recombinant gene deliveryvectors for treating or preventing lysosomal storage disorders.WO2000073482 (2000).
91. Desmaris N, Verot L, Puech JP, Caillaud C, Vanier MT, Heard J. M. Prevention of neuropathology in the mouse model of Hurlersyndrome. Ann Neurol 2004; 56: 68-76.
92. Hoogerbrugge PM, Brouwer OF, Bordigoni P, Ringden O, Kapaun P, Ortega JJ, et al. Allogeneic bone marrow transplantation forlysosomal storage diseases. The European Group for Bone MarrowTransplantation. Lancet 1995; 345: 1398-402.
93. Krivit W, Sung JH, Shapiro EG, Lockman LA. Microglia: The effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal andperoxisomal storage diseases. Cell Transplant 1995; 4: 385-92.
94. Krivit W, Peters C, Shapiro EG. Bone marrow transplantation aseffective treatment of central nervous system disease in globoidcell leukodystrophy, metachromatic leukodystrophy, adrenoleu-kodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher diseasetype III. Curr Opin Neurol 1999; 12: 167-76.
95. Orchard PJ, Blazar BR, Wagner J, Charnas L, Krivit W, Tolar J. Hematopoietic cell therapy for metabolic disease. J Pediatr 2007; 151: 340-6.
96. Kennedy DW, Abkowitz J. L. Kinetics of central nervous systemmicroglial and macrophage engraftment: Analysis using atransgenic bone marrow transplantation model. Blood 1997; 90:986-93.
97. Wynn RF, Wraith JE, Mercer J, O'Meara A, Tylee K, Thornley M, et al. Improved metabolic correction in patients with lysosomalstorage disease treated with hematopoietic stem cell transplantcompared with enzyme replacement therapy. J Pediatr 2009; 154:609-11.
98. Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, et al. Hematopoietic stem cell genetherapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 2009; 326: 818-23.
99. Biffi A, Lucchini G, Rovelli A, Sessa M. Metachromaticleukodystrophy: an overview of current and prospective treatments. Bone Marrow Transplant 2008; 42: S2-6. Review.
100. Deleyrolle LP, Reynolds BA. Isolation, expansion, anddifferentiation of adult Mammalian neural stem and progenitorcells using the neurosphere assay. Methods Mol Biol 2009; 549:91-101.
101. Snyder EY, Daley GQ, Goodell M. Taking stock and planning forthe next decade: Realistic prospects for stem cell therapies for thenervous system. J Neurosci Res 2004; 76: 157-68.
102. Guillaume DJ, Huhn SL, Selden NR, Steiner RD. Cellular therapyfor childhood neurodegenerative disease. Part I: Rationale and preclinical studies. Neurosurg Focus 2008; 24: E22.
103. Selden NR, Guillaume DJ, Steiner RD, Huhn SL. Cellular therapyfor childhood neurodegenerative disease. Part II: Clinical trialdesign and implementation. Neurosurg Focus 2008; 24: E23
104. Vanguri, P., Mosca, J.D. Intraperitoneal delivery of geneticallyengineered mesenchymal stem cells. WO2003101202 (2003).
105. Brooke G, Cook M, Blair C, Han R, Heazlewood C, Jones B, et al. Therapeutic applications of mesenchymal stromal cells. Semin CellDev Biol 2007; 18: 846-58.
106. Motaln H, Schichor C, Lah TT. Human mesenchymal stem cellsand their use in cell-based therapies. Cancer 116: 2519-30.
107. Blazar, B., Tolar, J., Verfaillie, C.M. Compositions and methodsfor the treatment of lysosomal storage disorders. WO2005056026(2005).
108. Ramaswami, M. Genetically modified somatic cells for sustainedsecretion of lysosomal proenzymes deficient in lysosomal storage disorders. WO2005021716 (2005).
109. Uchida, N., Jacobs, Y., Tamaki, S. Methods for the treatment oflysosomal storage disorders. WO2006074387 (2006).
110. Conti L, Cattaneo E. Neural stem cell systems: Physiologicalplayers or in vitro entities? Nat Rev Neurosci 2010; 11: 176-87.
111. Fan JQ. A contradictory treatment for lysosomal storage disorders:Inhibitors enhance mutant enzyme activity. Trends Pharmacol Sci 2003; 24: 355-60.
112. Pastores GM. Miglustat: Substrate reduction therapy for lysosomalstorage disorders associated with primary central nervous systeminvolvement. Recent Pat CNS Drug Discov 2006; 1: 77-82
113. Butters TD. Pharmacotherapeutic strategies using small moleculesfor the treatment of glycolipid lysosomal storage disorders. ExpertOpin Pharmacother 2007; 8: 427-35.
114. Lachmann RH, Platt FM. Substrate reduction therapy forglycosphingolipid storage disorders. Expert Opin Investig Drugs2001; 10: 455-66.
115. Platt FM, Neises GR, Dwek RA, Butters TD. N-butyldeoxy-nojirimycin is a novel inhibitor of glycolipid biosynthesis. J BiolChem 1994; 269: 8362-5.
116. Elstein D, Hollak C, Aerts JM, van Weely S, Maas M, Cox T. M., et al. Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease. J Inherit Metab Dis 2004; 27: 757-66.
117. Cox TM, Aerts JM, Andria G, Beck M, Belmatoug N, Bembi B, et al. The role of the iminosugar N-butyldeoxynojirimycin(miglustat) in the management of type I (non-neuronopathic)Gaucher disease: A position statement. J Inherit Metab Dis 2003; 26: 513-26.
118. Patterson MC, Vecchio D, Prady H, Abel L, Wraith JE. Miglustatfor treatment of Niemann-Pick C disease: A randomised controlledstudy. Lancet Neurol 2007; 6: 765-72.
119. Walkley, S. Mucopolysaccharidosis therapies. WO2002055064(2002).
120. Hirth, B.H., Siegel, C. Synthesis of UDP-glucose: N-Acylsphin-gosine glucosyltransferase inhibitors. WO2003008339 (2003).
121. McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang W. L, Hutto E, et al. A specific and potent inhibitor of glucosylceramidesynthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab 2007; 91: 259-67.
122. Roberts AL, Thomas BJ, Wilkinson AS, Fletcher JM, Byers S. Inhibition of glycosaminoglycan synthesis using rhodamine B in amouse model of mucopolysaccharidosis type III A. Pediatr Res 2006; 60: 309-14.
123. Roberts AL, Rees MH, Klebe S, Fletcher JM, Byers S. Improvement in behaviour after substrate deprivation therapy with rhodamine B in a mouse model of MPS III A. Mol Genet Metab 2007; 92: 115-21.
124. Grynkiewicz, G., Wegrzyn, G., Szechner, B., Szeja, W., Tylki-Szymanska, A., Wegrzyn, A., Jakobkiewicz-Banecka, J., Baranska, S., Czartoryska, B., Piotrowska, E. Isoflavones and theirderivatives in the treatment of mucopolysaccharidoses.WO2007035121 (2007).
125. Piotrowska E, Jakóbkiewicz-Banecka J, Bara ska S, Tylki-Szymaska A, Czartoryska B, Wegrzyn A, et al. Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis forgene expression-targeted isoflavone therapy for mucopoly-saccharidoses. Eur J Hum Genet 2006; 14: 846-52.
126. Malinowska M, Wilkinson FL, Bennett W, Langford-Smith K. J, O'Leary H.A' Jakobkiewicz-Banecka J, et al. Genistein reduceslysosomal storage in peripheral tissues of mucopolysaccharide IIIBmice. Mol Genet Metab 2009; 98: 235-42.
127. Fan JQ, Ishii S. Active-site-specific chaperone therapy for Fabrydisease. Yin and Yang of enzyme inhibitors. FEBS J 2007; 274:4962-71.
128. Arakawa T, Ejima D, Kita Y, Tsumoto K. Small moleculepharmacological chaperones: From thermodynamic stabilization topharmaceutical drugs. Biochim Biophys Acta 2006; 1764: 1677-87.
129. Yu Z, Sawkar AR, Kelly JW. Pharmacologic chaperoning as astrategy to treat Gaucher disease. FEBS J 2007; 274: 4944-50.
130. Matsuda J, Suzuki O, Oshima A, Yamamoto Y, Noguchi A.'Takimoto K., et al. Chemical chaperone therapy for brain pathologyin G(M1)-gangliosidosis. Proc Natl Acad Sci USA 2003; 100:15912-7.
131. Maegawa GH, Tropak M, Buttner J, Stockley T, Kok F, Clarke J. T' et al. Pyrimethamine as a potential pharmacological chaperone forlate-onset forms of GM2 gangliosidosis. J Biol Chem 2007; 282:9150-61.
132. Okumiya T, Kroos MA, Vliet LV, Takeuchi H, Van der Ploeg A. T.'Reuser A.J. Chemical chaperones improve transport and enhancestability of mutant alpha-glucosidases in glycogen storage diseasetype II. Mol Genet Metab 2007; 90: 49-57.
133. Schueler UH, Kolter T, Kaneski CR, Zirzow GC, Sandhoff K, Brady RO. Correlation between enzyme activity and substratestorage in a cell culture model system for Gaucher disease. J Inherit Metab Dis 2004; 27: 649-58.
134. Butters TD, Dwek RA, Platt F. M. Imino sugar inhibitors for treatingthe lysosomal glycosphingolipidoses. Glycobiology 2005; 15: 43R-52R.
135. Kornhaber GJ, Tropak MB, Maegawa GH, Tuske SJ, Coales S.J., Mahuran D.J., et al. Isofagomine induced stabilization ofglucocerebrosidase. ChemBioChem 2008; 9: 2643-9.
136. Fan JQ, Ishii S, Asano N, Suzuki Y. Accelerated transport andmaturation of lysosomal alpha-galactosidase A in Fabrylymphoblasts by an enzyme inhibitor. Nat Med 1999; 5: 112-115
137. Fan, J.Q., Ishii, S., Asano, N. Method for increasing the activity oflysosomal enzymes. US20070021381 (2007).
138. Wustman, B. Treatment of cns disorders associated with mutationsin genes encoding lysosomal enzymes.WO2006133446 (2006).
139. Wustman, B. Method for the treatment of neurological disorders byenhancing the activity of -glucocerebrosidase. WO2007150064(2007).
140. Lockhart, D. Treatment of Gaucher disease with specificpharmacological chaperones and monitoring treatment usingsurrogate markers. WO2008128106 (2008).
141. Palling, D. Method for the treatment of Fabry disease usingpharmacological chaperones. WO2008121826 (2008).
142. Lockhart, D., Wustman, B. Dosing regimens for the treatment oflysosomal storage diseases using pharmacological chaperones.WO2008134628 (2008).
143. Mugrage, B. Use of substrates as pharmacological chaperones.WO2008128089 (2008).
144. Wustman, B., Do H.V. Treatment of Pompe disease with specificpharmacological chaperones and monitoring treatment usingsurrogate markers. WO2009114679 (2009).
145. Do, H.V., Valenzano, K., Lockhart, D. Therapy regimens, dosingregimens and stable medicaments for the treatment of Pompedisease. WO2010056746 (2010).
146. Mahuran, D., Tropak, M., Withers, S. Treatment of Tay Sachs orSandhoff diseases by enhancing hexosaminidase activity.WO2004103368 (2004).
147. Mahuran, D.J., Tropak, M.B., Buttner, J., Blanchard, J.E., Brown, E. D. Compositions and methods for enhancing enzyme activity in Gaucher, GM1-gangliosidosis, Morquio N disease, and Parkinson'sdisease. WO2009049421 (2009) and WO2009049422 (2009).
148. Tropak MB, Mahuran D. Lending a helping hand, screeningchemical libraries for compounds that enhance beta-hexosa-minidase A activity in GM2 gangliosidosis cells. FEBS J 2007; 274: 4951-61. Review.
149. Clarke JT, Mahuran DJ, Sathe S, Kolodny EH, Rigat BA, Raiman J. A., et al. An open-label Phase I/II clinical trial of pyrimethaminefor the treatment of patients affected with chronic GM2gangliosidosis (Tay-Sachs or Sandhoff variants). Mol Genet Metab2010; (in press) doi:10.1016/j.ymgme.2010.09.004
150. Lingwood, C.A., McGrath, M.S., Azhir, A.A. Compositions andmethods for treating lysosomal disorders. WO2009073564 (2009).
151. Suzuki Y. Chemical chaperone therapy for GM1-gangliosidosis.Cell Mol Life Sci 2008; 65: 351-3. Review.
152. Ogawa, S., Suzuki, Y., Matsuda, J., Ohno, K. Carba-sugar aminederivatives and treatments of disorder of glycolipid metabolismcontaining the same as the active ingredient. WO2003022797(2003).
153. Wilson, F.X., Nash, R.J., Horne, G., Storer, R., Tinsley, J. M.'Roach, A. G. Treatment of lysosomal storage disorders and otherproteostatic diseases. WO2010015816 (2010).
154. Hopwood, J. Sulphated sugars to increase activity of sulphatases enlysosomal storage disorders.WO2010022461 (2010).
155. Garcia Fernandez, J.M., Ortiz Mellet, C., Garcia Moncayo, M.I., Suzuki, Y., Ohno, K., Aguilar Moreno, M. Compounds promotingthe activity of mutant glycosidases. WO2010046517 (2010).
156. Aerts, J.M.F.G. Deoxynojirimycin analogues and their uses asglucosylceramidase inhibitors. WO2005040118 (2005).
157. Horowitz, M., Ron Ronen, I. Methods of treating lysosomal storagedisorders. WO2009040816 (2009).
158. Grammatopoulos, T., Justman, C.J., Liu, Z., Lansbury, P. T., Cullen, V. C. Treatment of lysosomal storage diseases.WO2008112525 (2008).
159. Zheng W, Padia J, Urban DJ, Jadhav A, Goker-Alpan O, Simeonov, A., et al. Three classes of glucocerebrosidase inhibitors identifiedby quantitative high-throughput screening are chaperone leads forGaucher disease. Proc Natl Acad Sci USA 2007; 104: 13192-7.
160. Balch WE, Morimoto RI, Dillin A, Kelly JW. Adaptingproteostasis for disease intervention. Science 2008; 319: 916-9.
161. Mu TW, Ong DS, Wang YJ, Balch WE, Yates JR, 3rd, Segatori L, et al. Chemical and biological approaches synergize to ameliorateprotein-folding diseases. Cell 2008; 134: 769-81.
162. Ginns, E.I., Ostroff, G.R. Compositions and their uses forlysosomal enzyme deficiencies. WO2006032039 (2006).
163. Platt, F., Lloyd-Evans, E. Treating niemann-pick disease type Cand related disorders by elevating intracellular calcium.WO2009141627 (2009).