Skip to main content
SpringerLink
Log in

Therapeutic approaches for neuronopathic lysosomal storage disorders

  • LSDs with Neurologic Involvement
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Therapy of the central nervous system (CNS) manifestations of lysosomal storage diseases (LSDs) has remained a major challenge because of its inability to deliver therapeutic agents efficiently across the intact blood–brain barrier. Non-specific therapies such as hematopoietic stem cell transplantation have been useful in globoid cell leukodystrophy (Krabbe disease) and in some mucopolysaccharidoses. Anti-inflammatory agents also show promise as adjuvant therapy. High doses of replacement therapy with native or modified enzyme show renewed promise for correction of CNS cells. Alternatively, small molecules can enter the brain relatively easily and promote reduction of accumulated substrate or function as pharmacological chaperones to enhance the level of the deficient enzyme. Gene therapy is still being developed and tested in patients. It is therefore likely that, thanks to a better understanding of disease mechanism, a variety of therapeutic approaches, used alone or in combination, will be useful to treat the devastating neurological complications of LSDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37: 13–25

    Google Scholar 

  • ACOG Committee on Genetics (2009) ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. Obstet Gynecol 114:950–953

  • Abe A, Gregory S, Lee L, Killen PD, Brady RO, Kulkarni A, Shayman JA (2000) Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J Clin Invest 105:1563–1571

    Article  CAS  PubMed  Google Scholar 

  • Alvarez AR, Klein A, Castro J, Cancino GI, Amigo J, Mosqueira M, Vargas LM, Yevenes LF, Bronfman FC, Zanlungo S (2008) Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease. FASEB J 22:3617–3627

    Article  CAS  PubMed  Google Scholar 

  • Begley DJ, Pontikis CC, Scarpa M (2008) Lysosomal storage diseases and the blood-brain barrier. Curr Pharm Des 14:1566–1580

    Article  CAS  PubMed  Google Scholar 

  • Biffi A, De Palma M, Quattrini A, Del Carro U, Amadio S, Visigalli I, Sessa M, Fasano S, Brambilla R, Marchesini S, Bordignon C, Naldini L (2004) Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells. J Clin Invest 113:1118–1129

    CAS  PubMed  Google Scholar 

  • Biswas S, LeVine SM (2002) Substrate-reduction therapy enhances the benefits of bone marrow transplantation in young mice with globoid cell leukodystrophy. Pediatr Res 51:40–47

    Article  PubMed  Google Scholar 

  • Blanz J, Stroobants S, Lullmann-Rauch R, Morelle W, Ludemann M, D’Hooge R, Reuterwall H, Michalski JC, Fogh J, Andersson C, Saftig P (2008) Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in alpha-mannosidosis mice. Hum Mol Genet 17:3437–3445

    Article  CAS  PubMed  Google Scholar 

  • Boado RJ, Zhang Y, Xia CF, Wang Y, Pardridge WM (2008) Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood-brain barrier. Biotechnol Bioeng 99:475–484

    Article  CAS  PubMed  Google Scholar 

  • Brady RO (2006) Enzyme replacement for lysosomal diseases. Annu Rev Med 57:283–296

    Article  CAS  PubMed  Google Scholar 

  • Buechner S, Moretti M, Burlina AP, Cei G, Manara R, Ricci R, Mignani R, Parini R, Di Vito R, Giordano GP, Simonelli P, Siciliano G, Borsini W (2008) Central nervous system involvement in Anderson-Fabry disease: a clinical and MRI retrospective study. J Neurol Neurosurg Psychiatry 79:1249–1254

    Article  CAS  PubMed  Google Scholar 

  • Cearley CN, Wolfe JH (2007) A single injection of an adeno-associated virus vector into nuclei with divergent connections results in widespread vector distribution in the brain and global correction of a neurogenetic disease. J Neurosci 27:9928–9940

    Article  CAS  PubMed  Google Scholar 

  • Chen YH, Chang M, Davidson BL (2009) Molecular signatures of disease brain endothelia provide new sites for CNS-directed enzyme therapy. Nat Med 15:1215–1218

    Google Scholar 

  • Di Domenico C, Villani GR, Di Napoli D, Nusco E, Cali G, Nitsch L, Di Natale P (2009) Intracranial gene delivery of LV-NAGLU vector corrects neuropathology in murine MPS IIIB. Am J Med Genet 149A:1209–1218

    Article  PubMed  Google Scholar 

  • Dickson P, McEntee M, Vogler C, Le S, Levy B, Peinovich M, Hanson S, Passage M, Kakkis E (2007) Intrathecal enzyme replacement therapy: successful treatment of brain disease via the cerebrospinal fluid. Mol Genet Metab 91:61–68

    Article  CAS  PubMed  Google Scholar 

  • Dunder U, Kaartinen V, Valtonen P, Vaananen E, Kosma VM, Heisterkamp N, Groffen J, Mononen I (2000) Enzyme replacement therapy in a mouse model of aspartylglycosaminuria. FASEB J 14:361–367

    CAS  PubMed  Google Scholar 

  • Elliot-Smith E, Speak AO, Lloyd-Evans E, Smith DA, van der Spoel AC, Jeyakumar M, Butters TD, Dwek RA, d’Azzo A, Platt FM (2008) Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis. Mol Genet Metab 94:204–211

    Article  CAS  PubMed  Google Scholar 

  • Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J (2005) Transplantation of umbilical-cord blood in babies with infantile Krabbe’s disease. N Engl J Med 352:2069–2081

    Article  CAS  PubMed  Google Scholar 

  • Fan JQ, Ishii S (2007) Active-site-specific chaperone therapy for Fabry disease. Yin and Yang of enzyme inhibitors. FEBS J 274:4962–4971

    Article  CAS  PubMed  Google Scholar 

  • Fleming DR, Henslee-Downey PJ, Ciocci G, Romond EH, Marciniak E, Munn RK, Thompson JS (1998) The use of partially HLA-mismatched donors for allogeneic transplantation in patients with mucopolysaccharidosis-I. Pediatr Transplant 2:299–304

    CAS  PubMed  Google Scholar 

  • Fraldi A, Hemsley K, Crawley A, Lombardi A, Lau A, Sutherland L, Auricchio A, Ballabio A, Hopwood JJ (2007) Functional correction of CNS lesions in an MPS-IIIA mouse model by intracerebral AAV-mediated delivery of sulfamidase and SUMF1 genes. Hum Mol Genet 16:2693–2702

    Article  CAS  PubMed  Google Scholar 

  • Grubb JH, Vogler C, Levy B, Galvin N, Tan Y, Sly WS (2008a) Chemically modified beta-glucuronidase crosses blood-brain barrier and clears neuronal storage in murine mucopolysaccharidosis VII. Proc Natl Acad Sci U S A 105:2616–2621

    Article  CAS  PubMed  Google Scholar 

  • Grubb JH, Vogler C, Tan Y, Shah GN, MacRae AF, Sly WS (2008b) Infused Fc-tagged beta-glucuronidase crosses the placenta and produces clearance of storage in utero in mucopolysaccharidosis VII mice. Proc Natl Acad Sci U S A 105:8375–8380

    Article  CAS  PubMed  Google Scholar 

  • Gungor N, Tuncbilek E (1995) Sanfilippo disease type B. A case report and review of the literature on recent advances in bone marrow transplantation. Turk J Pediatr 37:157–163

    CAS  PubMed  Google Scholar 

  • Haskins M (2009) Gene therapy for lysosomal storage diseases (LSDs) in large animal models. ILAR J 50:112–121

    CAS  PubMed  Google Scholar 

  • Hemsley KM, King B, Hopwood JJ (2007) Injection of recombinant human sulfamidase into the CSF via the cerebellomedullary cistern in MPS IIIA mice. Mol Genet Metab 90:313–328

    Article  CAS  PubMed  Google Scholar 

  • Hemsley KM, Beard H, King BM, Hopwood JJ (2008) Effect of high dose, repeated intra-CSF injection of sulphamidase on neuropathology in MPS IIIA mice. Genes Brain Behav 7:740–753

    Google Scholar 

  • Hemsley KM, Luck AJ, Crawley AC, Hassiotis S, Beard H, King B, Rozek T, Rozaklis T, Fuller M, Hopwood JJ (2009) Examination of intravenous and intra-CSF protein delivery for treatment of neurological disease. Eur J NeuroSci 29:1197–1214

    Article  PubMed  Google Scholar 

  • Hilz MJ, Brys M, Marthol H, Stemper B, Dutsch M (2004) Enzyme replacement therapy improves function of C-, Adelta-, and Abeta-nerve fibers in Fabry neuropathy. Neurology 62:1066–1072

    CAS  PubMed  Google Scholar 

  • Jeyakumar M, Butters TD, Cortina-Borja M, Hunnam V, Proia RL, Perry VH, Dwek RA, Platt FM (1999) Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. Proc Natl Acad Sci U S A 96:6388–6393

    Article  CAS  PubMed  Google Scholar 

  • Jeyakumar M, Norflus F, Tifft CJ, Cortina-Borja M, Butters TD, Proia RL, Perry VH, Dwek RA, Platt FM (2001) Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation. Blood 97:327–329

    Article  CAS  PubMed  Google Scholar 

  • Jeyakumar M, Thomas R, Elliot-Smith E, Smith DA, van der Spoel AC, d’Azzo A, Perry VH, Butters TD, Dwek RA, Platt FM (2003) Central nervous system inflammation is a hallmark of pathogenesis in mouse models of GM1 and GM2 gangliosidosis. Brain 126:974–987

    Article  CAS  PubMed  Google Scholar 

  • Jeyakumar M, Smith DA, Williams IM, Borja MC, Neville DC, Butters TD, Dwek RA, Platt FM (2004) NSAIDs increase survival in the Sandhoff disease mouse: synergy with N-butyldeoxynojirimycin. Ann Neurol 56:642–649

    Article  CAS  PubMed  Google Scholar 

  • Kakkis E, McEntee M, Vogler C, Le S, Levy B, Belichenko P, Mobley W, Dickson P, Hanson S, Passage M (2004) Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I. Mol Genet Metab 83:163–174

    Article  CAS  PubMed  Google Scholar 

  • Kurai T, Hisayasu S, Kitagawa R, Migita M, Suzuki H, Hirai Y, Shimada T (2007) AAV1 mediated co-expression of formylglycine-generating enzyme and arylsulfatase A efficiently corrects sulfatide storage in a mouse model of metachromatic leukodystrophy. Mol Ther 15:38–43

    Article  CAS  PubMed  Google Scholar 

  • Lacorazza HD, Flax JD, Snyder EY, Jendoubi M (1996) Expression of human beta-hexosaminidase alpha-subunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells. Nat Med 2:424–429

    Article  CAS  PubMed  Google Scholar 

  • Laurie C, Reynolds A, Coskun O, Bowman E, Gendelman HE, Mosley RL (2007) CD4+ T cells from copolymer-1 immunized mice protect dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. J Neuroimmunol 183:60–68

    Article  CAS  PubMed  Google Scholar 

  • Lee WC, Courtenay A, Troendle FJ, Stallings-Mann ML, Dickey CA, DeLucia MW, Dickson DW, Eckman CB (2005) Enzyme replacement therapy results in substantial improvements in early clinical phenotype in a mouse model of globoid cell leukodystrophy. FASEB J 19:1549–1551

    Article  CAS  PubMed  Google Scholar 

  • Lee WC, Tsoi YK, Troendle FJ, DeLucia MW, Ahmed Z, Dicky CA, Dickson DW, Eckman CB (2007) Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophy. FASEB J 21:2520–2527

    Article  CAS  PubMed  Google Scholar 

  • Luzi P, Rafi MA, Zaka M, Rao HZ, Curtis M, Vanier MT, Wenger DA (2005) Biochemical and pathological evaluation of long-lived mice with globoid cell leukodystrophy after bone marrow transplantation. Mol Genet Metab 86:150–159

    Article  CAS  PubMed  Google Scholar 

  • Maegawa GH, Tropak M, Buttner J, Stockley T, Kok F, Clarke JT, Mahuran DJ (2007) Pyrimethamine as a potential pharmacological chaperone for late-onset forms of GM2 gangliosidosis. J Biol Chem 282:9150–9161

    Article  CAS  PubMed  Google Scholar 

  • Maegawa GH, Banwell BL, Blaser S, Sorge G, Toplak M, Ackerley C, Hawkins C, Hayes J, Clarke JT (2009) Substrate reduction therapy in juvenile GM2 gangliosidosis. Mol Genet Metab 98:215–224

    Article  CAS  PubMed  Google Scholar 

  • Malm D, Nilssen O (2008) Alpha-mannosidosis. Orphanet J Rare Dis 3:21

    Article  PubMed  Google Scholar 

  • Malm G, Gustafsson B, Berglund G, Lindstrom M, Naess K, Borgstrom B, von Dobeln U, Ringden O (2008) Outcome in six children with mucopolysaccharidosis type IH, Hurler syndrome, after haematopoietic stem cell transplantation (HSCT). Acta Paediatr 97:1108–1112

    Article  PubMed  Google Scholar 

  • Matzner U, Herbst E, Hedayati KK, Lullmann-Rauch R, Wessig C, Schroder S, Eistrup C, Moller C, Fogh J, Gieselmann V (2005) Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy. Hum Mol Genet 14:1139–1152

    Article  CAS  PubMed  Google Scholar 

  • Montano AM, Oikawa H, Tomatsu S, Nishioka T, Vogler C, Gutierrez MA, Oguma T, Tan Y, Grubb JH, Dung VC, Ohashi A, Miyamoto K, Orii T, Yoneda Y, Sly WS (2008) Acidic amino acid tag enhances response to enzyme replacement in mucopolysaccharidosis type VII mice. Mol Genet Metab 94:178–189

    Article  CAS  PubMed  Google Scholar 

  • Munoz-Rojas MV, Vieira T, Costa R, Fagondes S, John A, Jardim LB, Vedolin LM, Raymundo M, Dickson PI, Kakkis E, Giugliani R (2008) Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression. Am J Med Genet 146A:2538–2544

    Article  PubMed  Google Scholar 

  • Okuda T, Furukawa K, Nakayama K (2009) A novel, promoter-based, target-specific assay identifies 2-deoxy-D-glucose as an inhibitor of globotriaosylceramide biosynthesis. FEBS J 276:5191–5202

    Article  CAS  PubMed  Google Scholar 

  • Orchard PJ, Blazar BR, Wagner J, Charnas L, Krivit W, Tolar J (2007) Hematopoietic cell therapy for metabolic disease. J Pediatr 151:340–346

    Article  PubMed  Google Scholar 

  • Passini MA, Bu J, Fidler JA, Ziegler RJ, Foley JW, Dodge JC, Yang WW, Clarke J, Taksir TV, Griffiths DA, Zhao MA, O’Riordan CR, Schuchman EH, Shihabuddin LS, Cheng SH (2007) Combination brain and systemic injections of AAV provide maximal functional and survival benefits in the Niemann-Pick mouse. Proc Natl Acad Sci U S A 104:9505–9510

    Article  CAS  PubMed  Google Scholar 

  • Pastores GM, Barnett NL, Kolodny EH (2005) An open-label, noncomparative study of miglustat in type I Gaucher disease: efficacy and tolerability over 24 months of treatment. Clin Ther 27:1215–1227

    Article  CAS  PubMed  Google Scholar 

  • Patterson MC, Vecchio D, Prady H, Abel L, Wraith JE (2007) Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study. Lancet Neurol 6:765–772

    Article  CAS  PubMed  Google Scholar 

  • Pelled D, Lloyd-Evans E, Riebeling C, Jeyakumar M, Platt FM, Futerman AH (2003) Inhibition of calcium uptake via the sarco/endoplasmic reticulum Ca2+-ATPase in a mouse model of Sandhoff disease and prevention by treatment with N-butyldeoxynojirimycin. J Biol Chem 278:29496–29501

    Article  CAS  PubMed  Google Scholar 

  • Pelled D, Trajkovic-Bodennec S, Lloyd-Evans E, Sidransky E, Schiffmann R, Futerman AH (2005) Enhanced calcium release in the acute neuronopathic form of Gaucher disease. Neurobiol Dis 18:83–88

    Article  CAS  PubMed  Google Scholar 

  • Peters C, Balthazor M, Shapiro EG, King RJ, Kollman C, Hegland JD, Henslee-Downey J, Trigg ME, Cowan MJ, Sanders J, Bunin N, Weinstein H, Lenarsky C, Falk P, Harris R, Bowen T, Williams TE, Grayson GH, Warkentin P, Sender L, Cool VA, Crittenden M, Packman S, Kaplan P, Lockman LA, Anderson J, Krivit W, Dusenbery K, Wagner J (1996) Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 87:4894–4902

    CAS  PubMed  Google Scholar 

  • Peters C, Shapiro EG, Krivit W (1998) Neuropsychological development in children with Hurler syndrome following hematopoietic stem cell transplantation. Pediatr Transplant 2:250–253

    CAS  PubMed  Google Scholar 

  • Pierson TM, Bonnemann CG, Finkel RS, Bunin N, Tennekoon GI (2008) Umbilical cord blood transplantation for juvenile metachromatic leukodystrophy. Ann Neurol 64:583–587

    Article  PubMed  Google Scholar 

  • Platt FM, Jeyakumar M (2008) Substrate reduction therapy. Acta Paediatr Suppl 97:88–93

    Article  PubMed  Google Scholar 

  • Platt FM, Neises GR, Reinkensmeier G, Townsend MJ, Perry VH, Proia RL, Winchester B, Dwek RA, Butters TD (1997) Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin. Science 276:428–431

    Article  CAS  PubMed  Google Scholar 

  • Prasad VK, Kurtzberg J (2008) Emerging trends in transplantation of inherited metabolic diseases. Bone Marrow Transplant 41:99–108

    Article  CAS  PubMed  Google Scholar 

  • Rafi MA, Zhi Rao H, Passini MA, Curtis M, Vanier MT, Zaka M, Luzi P, Wolfe JH, Wenger DA (2005) AAV-mediated expression of galactocerebrosidase in brain results in attenuated symptoms and extended life span in murine models of globoid cell leukodystrophy. Mol Ther 11:734–744

    Article  CAS  PubMed  Google Scholar 

  • Ries M, Clarke JT, Whybra C, Timmons M, Robinson C, Schlaggar BL, Pastores G, Lien YH, Kampmann C, Brady RO, Beck M, Schiffmann R (2006) Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease. Pediatrics 118:924–932

    Article  PubMed  Google Scholar 

  • Sands MS, Haskins ME (2008) CNS-directed gene therapy for lysosomal storage diseases. Acta Paediatr Suppl 97:22–27

    Article  PubMed  Google Scholar 

  • Sano R, Tessitore A, Ingrassia A, d’Azzo A (2005) Chemokine-induced recruitment of genetically modified bone marrow cells into the CNS of GM1-gangliosidosis mice corrects neuronal pathology. Blood 106:2259–2268

    Article  CAS  PubMed  Google Scholar 

  • Savas PS, Hemsley KM, Hopwood JJ (2004) Intracerebral injection of sulfamidase delays neuropathology in murine MPS-IIIA. Mol Genet Metab 82:273–285

    Article  CAS  PubMed  Google Scholar 

  • Schiffmann R (2009) Fabry disease. Pharmacol Ther 122:65–77

    Article  CAS  PubMed  Google Scholar 

  • Schiffmann R, Heyes MP, Aerts JM, Dambrosia JM, Patterson MC, DeGraba T, Parker CC, Zirzow GC, Oliver K, Tedeschi G, Brady RO, Barton NW (1997) Prospective study of neurological responses to treatment with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher’s disease. Ann Neurol 42:613–621

    Article  CAS  PubMed  Google Scholar 

  • Schiffmann R, Floeter MK, Dambrosia JM, Gupta S, Moore DF, Sharabi Y, Khurana RK, Brady RO (2003) Enzyme replacement therapy improves peripheral nerve and sweat function in Fabry disease. Muscle Nerve 28:703–710

    Article  CAS  PubMed  Google Scholar 

  • Schiffmann R, Ries M, Timmons M, Flaherty JT, Brady RO (2006) Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. Nephrol Dial Transplant 21:345–354

    Article  CAS  PubMed  Google Scholar 

  • Schiffmann R, Fitzgibbon EJ, Harris C, DeVile C, Davies EH, Abel L, van Schaik IN, Benko W, Timmons M, Ries M, Vellodi A (2008) Randomized, controlled trial of miglustat in Gaucher’s disease type 3. Ann Neurol 64:514–522

    Article  PubMed  Google Scholar 

  • Schrijver I, Kulm M, Gardner PI, Pergament EP, Fiddler MB (2007) Comprehensive arrayed primer extension array for the detection of 59 sequence variants in 15 conditions prevalent among the (Ashkenazi) Jewish population. J Mol Diagnostics 9:228–236

    Article  CAS  Google Scholar 

  • Smith D, Wallom KL, Williams IM, Jeyakumar M, Platt FM (2009) Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1. Neurobiol Dis 36:242–251

    Google Scholar 

  • Sobrado M, Pereira MP, Ballesteros I, Hurtado O, Fernandez-Lopez D, Pradillo JM, Caso JR, Vivancos J, Nombela F, Serena J, Lizasoain I, Moro MA (2009) Synthesis of lipoxin A4 by 5-lipoxygenase mediates PPARgamma-dependent, neuroprotective effects of rosiglitazone in experimental stroke. J Neurosci 29:3875–3884

    Article  CAS  PubMed  Google Scholar 

  • Spencer BJ, Verma IM (2007) Targeted delivery of proteins across the blood-brain barrier. Proc Natl Acad Sci U S A 104:7594–7599

    Article  CAS  PubMed  Google Scholar 

  • Suzuki Y (2008) Chemical chaperone therapy for GM1-gangliosidosis. Cell Mol Life Sci 65:351–353

    Article  CAS  PubMed  Google Scholar 

  • Tansey MG, Goldberg MS (2009) Neuroinflammation in Parkinson’s disease: its role in neuronal death and implications for therapeutic intervention. Neurobiol Dis (in press)

  • Tolar J, Grewal SS, Bjoraker KJ, Whitley CB, Shapiro EG, Charnas L, Orchard PJ (2008) Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome. Bone Marrow Transplant 41:531–535

    Article  CAS  PubMed  Google Scholar 

  • Wada R, Tifft CJ, Proia RL (2000) Microglial activation precedes acute neurodegeneration in Sandhoff disease and is suppressed by bone marrow transplantation. Proc Natl Acad Sci U S A 97:10954–10959

    Article  CAS  PubMed  Google Scholar 

  • Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, Desnick RJ, Germain DP (2004) Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 75:65–74

    Article  CAS  PubMed  Google Scholar 

  • Worgall S, Sondhi D, Hackett NR, Kosofsky B, Kekatpure MV, Neyzi N, Dyke JP, Ballon D, Heier L, Greenwald BM, Christos P, Mazumdar M, Souweidane MM, Kaplitt MG, Crystal RG (2008) Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA. Hum Gene Ther 19:463–474

    Article  CAS  PubMed  Google Scholar 

  • Zervas M, Somers KL, Thrall MA, Walkley SU (2001) Critical role for glycosphingolipids in Niemann-Pick disease type C. Curr Biol 11:1283–1287

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, 75226, USA

    Raphael Schiffmann

Authors
  1. Raphael Schiffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raphael Schiffmann.

Additional information

Competing interest: R. Schiffmann received research grants and/or honoraria from Amicus Therapeutics, Shire Human Genetic Therapies and Genzyme Corporation.

Communicated by: Gregory Pastores

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schiffmann, R. Therapeutic approaches for neuronopathic lysosomal storage disorders. J Inherit Metab Dis 33, 373–379 (2010). https://doi.org/10.1007/s10545-010-9047-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-010-9047-0

Keywords

Search

Navigation