Lysosomal Storage Diseases To date

Abstract

New therapeutic options and progress of approved therapies have made Lysosomal Storage Diseases (LSDs) one of the most exciting group of diseases. This review aims to summarize current achievements in these particular disorders and to give an outlook towards possible future treatment options. Enzyme replacement therapy is the gold standard for Gaucher disease, Fabry disease, Mucopolysaccharidosis type I, II, and VI, and for Pompe disease. Besides this, substrate reduction has been approved for Gaucher disease and Niemann-Pick disease type C. However, clinical outcome in particular for neurologic affection in these disorders has been disappointing. In selected patients, bone marrow or stem cell transplantation may be beneficial. Whether or not, treatment with pharmaceutical chaperones may be able to improve in particular the neurologic outcome, remains open. Animal studies on gene therapy were promising, however, clinical application will need several years.

Keywords

• lysosome, Fabry disease, Gaucher disease, mucopolysaccharidosis, enzyme replacement therapy, substrate reduction therapy, chaperone

References

1. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA ; 281: 249-54. Beutler E, Grabowski GA. Gaucher disease. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001. p. 3635-69.
2. Campbell PE, Harris CM, Harris CM, Sirimanna T, Vellodi A. A model of neuronopathic Gaucher disease. J Inherit Metab Dis 2003; 26: 629-39.
3. Campbell PE, Harris CM, Vellodi A. Deterioration of the auditory brainstem response in children with type 3 Gaucher disease. Neurology 2004; 63: 7.
4. Goker-Alpan O, Wiggs EA, Eblan MJ, Benko W, Ziegler SG, Sidransky E et al. Cognitive outcome in treated patients with chronic neuronopathic Gaucher disease. J Pediatr 2008; 153: 89-94.
5. Brady RO, Pentchev PG, Gal AE, Hibbert SR, Dekaban AS. Replacement therapy for inherited enzyme glucocerebrosidase in Gaucher's disease. N Engl J Med 1974; 291: 989-93. Use of purified
6. Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC et al. Replacement therapy for inherited enzyme deficiency--macrophage- cerebrosidase for Gaucher's disease. N Engl J Med 1991; 324: 1464-70. targeted gluco
7. Weinreb NJ, Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med 2002; 113: 112-9.
8. Goker-Alpan O, Wiggs EA, Eblan MJ, Benko W, Ziegler SG, Sidransky E et al. Cognitive outcome in treated patients with chronic neuronopathic Gaucher disease. J Pediatr 2008; 153: 89-94.

9. Cox T, Lachmann R, Hollak C, Aerts J, van Weely S, Hrebicek M et al. Novel oral treatment of butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet 2000; 355: 1481-5.
10. Schiffmann R, Fitzgibbon EJ, Harris C, DeVile C, Davies EH, Abel L et al. Randomized, controlled trial of miglustat in Gaucher's disease type 3. Ann Neurol 2008; 64: 514-22.
11. Aviezer D, Brill-Almon E, Shaaltiel Y, Hashmueli S, Bartfeld D, Mizrachi S et al. A plant-derived glucocerebrosidase enzyme--a preclinical and phase I investigation. PLoS One 2009; 4: e4792.
12. Lukina E, Watman N, Arreguin EA, Banikazemi M, Dragosky M, Iastrebner M et al. A Phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood 2010 May 3.
13. Khanna R, Benjamin ER, Pellegrino L, Schilling A, Rigat BA, Soska R et al. The pharmacological chaperone isofagomine increases the activity of the Gaucher disease L444P mutant form of beta- glucosidase. FEBS J 2010; 277: 1618-38.
14. Deegan P, Baehner AF, Barba-Romero MA, Hughes D, Kampmann C, Beck M. Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet 2006; 43: 347-52.
15. Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U et al. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab 2008; 93: 112-28.
16. Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan G, Sakuraba H et al. High incidence of later-onset fabry disease revealed by newborn screening. Am J Hum Genet 2006; 79: 31-40.
17. Desnick RJ, Ioannou YA, Eng CM. alpha- Galactosidase A Deficiency: Fabry disease. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The Meatbolic & Molecular Bases of Inherited Disease. 8th Edition ed. New York: McGraw- Hill; 2001. p. 3733-810.
18. Schiffmann R, Kopp JB, Austin HA, III, Sabnis S, Moore DF, Weibel T et al. Enzyme replacement therapy in Fabry disease: a randomized controlled trial. JAMA 2001; 285: 9.
19. Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S et al. Safety and efficacy of recombinant human alpha-galactosidase A-- replacement therapy in Fabry's disease. N Engl J Med 2001; 345: 9-16.
20. Hughes DA, Elliott PM, Shah J, Zuckerman J, Coghlan G, Brookes J et al. Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double- blind, agalsidase alfa. Heart 2008; 94: 153-8. clinical trial of
21. Linhart A, Kampmann C, Zamorano JL, Sunder- Plassmann G, Beck M, Mehta A et al. Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. Eur Heart J 2007; 28: 1228-35.
22. Spinelli L, Pisani A, Sabbatini M, Petretta M, Andreucci MV, Procaccini D et al. Enzyme replacement improves cardiac involvement in Fabry's disease. Clin Genet 2004; 66: 158-65. agalsidase beta
23. Feriozzi S, Schwarting A, Sunder-Plassmann G, West M, Cybulla M. Agalsidase Alfa Slows the Decline in Renal Function in Patients with Fabry Disease. Am J Nephrol 2008; 29: 353-61.
24. Germain DP, Waldek S, Banikazemi M, Bushinsky DA, Charrow J, Desnick RJ et al. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol 2007; 18: 1547
25. Hoffmann B, Schwarz M, Mehta A, Keshav S. Gastrointestinal symptoms in 342 patients with Fabry disease: prevalence and response to enzyme replacement therapy. Clin Gastroenterol Hepatol 2007; 5: 1447-53.
26. Hoffmann B, Beck M, Sunder-Plassmann G, Borsini W, Ricci R, Mehta A. Nature and prevalence of pain in Fabry disease and its response to enzyme replacement therapy--a retrospective analysis from the Fabry Outcome Survey. Clin J Pain 2007; 23: 535-42.
27. Hegemann S, Hajioff D, Conti G, Beck M, Sunder-Plassmann G, Widmer U et al. Hearing loss in Fabry disease: data from the Fabry Outcome Survey. Eur J Clin Invest 2006; 36: 654
28. Palla A, Hegemann S, Widmer U, Straumann D. Vestibular and auditory deficits in Fabry disease and their response to enzyme replacement therapy. J Neurol 2007; 254: 1433-42.
29. Schiffmann R, Floeter MK, Dambrosia JM, Gupta S, Moore DF, Sharabi Y et al. Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve 2003; 28: 703-10.
30. Hoffmann B, Garcia DL, Mehta A, Beck M, Widmer U, Ricci R. Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey). J Med Genet ; 42: 247-52. Baehner F, Kampmann C, Whybra C, Miebach E, Wiethoff CM, Beck M. Enzyme replacement therapy in heterozygous females with Fabry disease: results of a phase IIIB study. J Inherit Metab Dis 2003; 26: 617-27.
31. Ramaswami U, Wendt S, Pintos-Morell G, Parini R, Whybra C, Leon Leal JA et al. Enzyme replacement therapy with agalsidase alfa in children with Fabry disease. Acta Paediatr 2007; : 122-7.
32. Wraith JE, Tylki-Szymanska A, Guffon N, Lien YH, Tsimaratos M, Vellodi A et al. Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr ; 152: 563-70. Benjamin ER, Flanagan JJ, Schilling A, Chang HH, Agarwal L, Katz E chaperone pharmacological deoxygalactonojirimycin galactosidase A levels in Fabry patient cell lines. J Inherit Metab Dis 2009; 32: 424-40. alpha
33. Schwartz IV, Ribeiro MG, Mota JG, Toralles MB, Correia P, Horovitz D et al. A clinical study of 77 patients with mucopolysaccharidosis type II. Acta Paediatr Suppl 2007; 96: 63-70. Neufeld mucopolysaccharidoses. In: Scriver C, Beaudet
34. A, Sly W, Valle D, editors. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill; 2001. p. 3421-52. The Schwartz IV, Ribeiro MG, Mota JG, Toralles
35. MB, Correia P, Horovitz D et al. A clinical study of 77 patients with mucopolysaccharidosis type II. Acta Paediatr Suppl 2007; 96: 63-70.
36. Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics 2009; 123: 40.
37. Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics 2009; 123: 40.
38. Thomas JA, Jacobs S, Kierstein J, Van Hove J. Outcome after three years of laronidase enzyme replacement therapy in a patient with Hurler syndrome. J Inherit Metab Dis 2006; 29: 762.
39. Mercimek-Mahmutoglu S, Reilly C, Human D, Waters PJ, Stoeckler-Ipsiroglu S. Progression of organ manifestations upon enzyme replacement therapy in a patient with mucopolysaccharidosis type I/Hurler. World J Pediatr 2009; 5: 319-21.
40. Remerand G, Merlin E, Froissart R, Brugnon F, Kanold J, Janny L et al. Four successful pregnancies mucopolysaccharidosis allogeneic bone marrow transplantation. J Inherit Metab Dis 2009 March 13. patient I by treated
41. Wynn RF, Wraith JE, Mercer J, O'Meara A, Tylee K, Thornley M et al. Improved metabolic correction in patients with lysosomal storage disease treated with hematopoietic stem cell transplant compared with enzyme replacement therapy. J Pediatr 2009; 154: 609-11.
42. Boelens JJ, Rocha V, Aldenhoven M, Wynn R, O'Meara A, Michel G et al. Risk factor analysis after of transplantation in patients with hurler syndrome. Biol Blood Marrow Transplant 2009; 15: 618-25.
43. Bijarnia S, Shaw P, Vimpani A, Smith R, Pacey V, O'Grady H et al. Combined enzyme replacement and haematopoietic stem cell transplantation in Hurler syndrome. J Paediatr Child Health 2009; 45: 469-72.
44. Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med 2006; 8: 465-73.
45. Harmatz P, Giugliani R, Schwartz I, Guffon N, Teles EL, Miranda MC et al. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo- controlled, multinational study of recombinant human (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr 2006; 148: 533-9. sulfatase
46. Harmatz P, Giugliani R, Schwartz IV, Guffon N, Teles EL, Miranda MC et al. Long-term follow- up of endurance and safety outcomes during enzyme mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N- acetylgalactosamine 4-sulfatase. Mol Genet Metab 2008; 94: 469-75. therapy for
47. Harmatz P, Yu ZF, Giugliani R, Schwartz IV, Guffon N, Teles EL et al. Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated acetylgalactosamine 4-sulfatase. J Inherit Metab Dis 2010; 33: 51-60. human N
48. Pitz S, Ogun O, Arash L, Miebach E, Beck M. Does enzyme replacement therapy influence the ocular mucopolysaccharidosis? Graefes Arch Clin Exp Ophthalmol 2009; 247: 975-80. type VI
49. McGill JJ, Inwood AC, Coman DJ, Lipke ML, de Lore D, Swiedler SJ et al. Enzyme replacement therapy for mucopolysaccharidosis VI from 8 weeks of age--a sibling control study. Clin Genet ; 77: 492-8. Wang CC, Hwu WL, Lin KH. Long-term follow- up of a girl with Maroteaux-Lamy syndrome after bone marrow transplantation. World J Pediatr ; 4: 152-4. Bagewadi S, Roberts J, Mercer J, Jones S, Stephenson J, Wraith JE. Home treatment with Elaprase and Naglazyme is safe in patients with mucopolysaccharidoses respectively. J Inherit Metab Dis 2008; 31: 733-7. types II and VI,
50. Munoz-Rojas MV, Vieira T, Costa R, Fagondes S, John A, Jardim LB et al. Intrathecal enzyme replacement therapy in a patient with R et al. pharmacological characterization of different recombinant acid alpha-glucosidase preparations evaluated for the treatment of Pompe disease. Mol Genet Metab 2008; 94: 448-55. and Kishnani PS, Hwu WL, Mandel H, Nicolino M,
51. Yong F, Corzo D. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 2006; : 671-6.
52. Chen LR, Chen CA, Chiu SN, Chien YH, Lee NC, Lin MT et al. Reversal of cardiac dysfunction after enzyme replacement in patients with infantile-onset Pompe disease. J Pediatr ; 155: 271-5. Kishnani PS, Corzo D, Leslie ND, Gruskin D, van der PA, Clancy JP et al. Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res 2009; : 329-35.
53. Chien YH, Lee NC, Thurberg BL, Chiang SC, Zhang XK, Keutzer J et al. Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics 2009; : e1116-e1125.
54. Chien YH, Lee NC, Peng SF, Hwu WL. Brain development in infantile-onset Pompe disease treated by enzyme replacement therapy. Pediatr Res 2006; 60: 349-52.
55. Nicolino M, Byrne B, Wraith JE, Leslie N, Mandel H, Freyer DR et al. Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease. Genet Med 2009; 11: 210-9.
56. Strothotte S, Strigl-Pill N, Grunert B, Kornblum C, Eger K, Wessig C et al. Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12- month results of an observational clinical trial. J Neurol 2010; 257: 91-7.
57. Yanovitch TL, Casey R, Banugaria SG, Kishnani PS. Improvement of Bilateral Ptosis on Higher Dose Enzyme Replacement Therapy in Pompe Disease. J Neuroophthalmol 2010 April 16.
58. Kishnani PS, Corzo D, Leslie ND, Gruskin D, van der PA, Clancy JP et al. Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease. Pediatr Res 2009; : 329-35.
59. Sun B, Young SP, Li P, Di C, Brown T, Salva MZ et al. Correction of multiple striated muscles in murine Pompe disease through adeno- associated virus-mediated gene therapy. Mol Ther ; 16: 1366-71.
60. Porto C, Cardone M, Fontana F, Rossi B, Tuzzi MR, Tarallo A et al. The pharmacological chaperone N-butyldeoxynojirimycin enhances enzyme replacement therapy in Pompe disease fibroblasts. Mol Ther 2009; 17: 964-71.
61. Flanagan JJ, Rossi B, Tang K, Wu X, Mascioli K, Donaudy F et al. The pharmacological chaperone deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase. Hum Mutat 2009; 30: 92. van Til NP, Stok M, Aerts Kaya FS, de Waard
62. MC, Farahbakhshian E, Visser TP et al. Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype. Blood April 12. Richard E, Douillard-Guilloux G, Batista L, Caillaud C. Correction of glycogenosis type 2 by muscle-specific lentiviral vector. In Vitro Cell Dev Biol Anim 2008; 44: 397-406.
63. Patterson MC, Vecchio D, Prady H, Abel L, Wraith JE. Miglustat for treatment of Niemann- Pick C disease: a randomised controlled study. Lancet Neurol 2007; 6: 765-72.
64. Patterson MC, Vecchio D, Jacklin E, Abel L, Chadha-Boreham H, Luzy C et al. Long-term miglustat therapy in children with Niemann-Pick disease type C. J Child Neurol 2010; 25: 300-5.
65. Wraith JE, Vecchio D, Jacklin E, Abel L, Chadha-Boreham H, Luzy C et al. Miglustat in adult and juvenile patients with Niemann-Pick disease type C: long-term data from a clinical trial. Mol Genet Metab 2010; 99: 351-7.
66. Schlander M, Beck M. Expensive drugs for rare disorders: to treat or not to treat? The case of enzyme mucopolysaccharidosis VI. Curr Med Res Opin ; 25: 1285-93. therapy for