A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise
Main Article Content
Abstract
Mucopolysaccharidoses III (MPS III, Sanfilippo syndrome) is a subtype of the Mucopolysaccharidoses (MPS), a group of inherited lysosomal disorders caused by a deficiency of lysosomal enzymes responsible for catabolizing glycosaminoglycans (GAGs). Although MPS III is rare, MPS diseases as a group are relatively frequent with an overall incidence of approximately 1 in 20,000 – 25,000 births. MPS III are paediatric diseases, which cause learning difficulties, behavioural disorders and dementia, as well as skeletal deformities and ultimately result in premature death. There are currently no approved treatments for MPS III, but a number of therapeutic approaches are under development. In the past 30 years, research using cellular and animal models have led to clinical trials involving enzyme replacement therapy (ERT), substrate reduction therapy (SRT) and gene therapy, while stem cells approaches remain at the pre-clinical stage. Although safety and clinical efficacy in animal models have shown promise, the results of clinical trials have proved costly and shown limited therapeutic effects. In this review, we describe the progress that has been made for ERT, SRT, gene therapy and stem cell therapies, highlighting the obstacles and work that needs to be done to bring us closer to a real treatment for these devastating diseases.
Keywords:
Mucopolysaccharidoses III, Sanfilippo syndrome, lysosomal storage disease, neurodegeneration, enzyme replacement therapy, gene therapy, substrate reduction therapy, stem cell therapy, clinical trial
Article Details
How to Cite
PEARSE, Yewande; IACOVINO, Michelina.
A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise.
Medical Research Archives, [S.l.], v. 8, n. 2, feb. 2020.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2045>. Date accessed: 27 dec. 2024.
doi: https://doi.org/10.18103/mra.v8i2.2045.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Andrade F, Aldamiz-Echevarria L, Llarena M, Couce ML. Sanfilippo syndrome: Overall review. Pediatr. Int. Jun 2015;57(3):331-338.
2. Fedele AO. Sanfilippo syndrome: causes, consequences, and treatments. The application of clinical genetics. 2015;8:269-281.
3. Jakobkiewicz-Banecka J, Gabig-Ciminska M, Kloska A, et al. Glycosaminoglycans and mucopolysaccharidosis type III. Frontiers in bioscience (Landmark edition). Jun 1 2016;21:1393-1409.
4. Kresse H, Neufeld EF. The Sanfilippo A corrective factor. Purification and mode of action. J. Biol. Chem. Apr 10 1972;247(7):2164-2170.
5. von Figura K. Human alpha-n-acetylglucosaminidase. 2. Activity towards natural substrates and multiple recognition forms. Eur. J. Biochem. Nov 1 1977;80(2):535-542.
6. Klein U, Kresse H, von Figura K. Sanfilippo syndrome type C: deficiency of acetyl-CoA:alpha-glucosaminide N-acetyltransferase in skin fibroblasts. Proc. Natl. Acad. Sci. U. S. A. Oct 1978;75(10):5185-5189.
7. Kowalewski B, Lamanna WC, Lawrence R, et al. Arylsulfatase G inactivation causes loss of heparan sulfate 3-O-sulfatase activity and mucopolysaccharidosis in mice. Proc. Natl. Acad. Sci. U. S. A. Jun 26 2012;109(26):10310-10315.
8. Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA. Sanfilippo syndrome: a mini-review. J. Inherit. Metab. Dis. Apr 2008;31(2):240-252.
9. Cross EM, Hare DJ. Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders. J. Inherit. Metab. Dis. Mar 2013;36(2):189-200.
10. Lyon GK, E.H. Pastores, G.M. Neurology of Hereditary Metabolic Diseases of Children. 3 ed. New York: Mc Graw Hill; 2006.
11. Wraith JE. Mucopolysaccharidoses and Oligosaccharidoses. In: Fernandes J, Saudubray J-M, van den Berghe G, Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. Berlin, Heidelberg: Springer Berlin Heidelberg; 2006:495-507.
12. Giugliani R, Federhen A, Vairo F, et al. Emerging drugs for the treatment of mucopolysaccharidoses. Expert opinion on emerging drugs. 2016;21(1):9-26.
13. Gaffke L, Pierzynowska K, Piotrowska E, Wegrzyn G. How close are we to therapies for Sanfilippo disease? Metab. Brain Dis. Feb 2018;33(1):1-10.
14. Lancaster MA, Knoblich JA. Generation of cerebral organoids from human pluripotent stem cells. Nat. Protoc. Oct 2014;9(10):2329-2340.
15. Allende ML, Cook EK, Larman BC, et al. Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation. J. Lipid Res. Mar 2018;59(3):550-563.
16. Camp JG, Badsha F, Florio M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl. Acad. Sci. U. S. A. Dec 22 2015;112(51):15672-15677.
17. Cederquist GY, Asciolla JJ, Tchieu J, et al. Specification of positional identity in forebrain organoids. Nat. Biotechnol. Apr 2019;37(4):436-444.
18. Choi SH, Kim YH, Hebisch M, et al. A three-dimensional human neural cell culture model of Alzheimer's disease. Nature. Nov 13 2014;515(7526):274-278.
19. Jo J, Xiao Y, Sun AX, et al. Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons. Cell stem cell. Aug 4 2016;19(2):248-257.
20. Vallejo S, Fleischer A, Martin JM, Sanchez A, Palomino E, Bachiller D. Generation of two induced pluripotent stem cells lines from Mucopolysaccharydosis IIIA patient: IMEDEAi004-A and IMEDEAi004-B. Stem cell research. Oct 2018;32:110-114.
21. Vallejo-Diez S, Fleischer A, Martin-Fernandez JM, Sanchez-Gilabert A, Bachiller D. Generation of two induced pluripotent stem cells lines from a Mucopolysaccharydosis IIIB (MPSIIIB) patient. Stem cell research. Dec 2018;33:180-184.
22. Ghosh A, Shapiro E, Rust S, et al. Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III. Orphanet J. Rare Dis. Jun 26 2017;12(1):117.
23. Platt FM, Butters TD. Substrate Reduction Therapy. Lysosomal Storage Disorders. Boston, MA: Springer US; 2007:153-168.
24. Dziedzic D, Wegrzyn G, Jakobkiewicz-Banecka J. Impairment of glycosaminoglycan synthesis in mucopolysaccharidosis type IIIA cells by using siRNA: a potential therapeutic approach for Sanfilippo disease. Eur. J. Hum. Genet. Feb 2010;18(2):200-205.
25. Kaidonis X, Liaw WC, Roberts AD, Ly M, Anson D, Byers S. Gene silencing of EXTL2 and EXTL3 as a substrate deprivation therapy for heparan sulphate storing mucopolysaccharidoses. Eur. J. Hum. Genet. Feb 2010;18(2):194-199.
26. Canals I, Beneto N, Cozar M, Vilageliu L, Grinberg D. EXTL2 and EXTL3 inhibition with siRNAs as a promising substrate reduction therapy for Sanfilippo C syndrome. Sci. Rep. Sep 8 2015;5:13654.
27. Pisano MM, Greene RM. Epidermal growth factor potentiates the induction of ornithine decarboxylase activity by prostaglandins in embryonic palate mesenchymal cells: effects on cell proliferation and glycosaminoglycan synthesis. Dev. Biol. Aug 1987;122(2):419-431.
28. Tirone E, D'Alessandris C, Hascall VC, Siracusa G, Salustri A. Hyaluronan synthesis by mouse cumulus cells is regulated by interactions between follicle-stimulating hormone (or epidermal growth factor) and a soluble oocyte factor (or transforming growth factor beta1). J. Biol. Chem. Feb 21 1997;272(8):4787-4794.
29. Jakobkiewicz-Banecka J, Piotrowska E, Narajczyk M, Baranska S, Wegrzyn G. Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway. J. Biomed. Sci. Mar 2 2009;16:26.
30. Malinowska M, Wilkinson FL, Langford-Smith KJ, et al. Genistein improves neuropathology and corrects behaviour in a mouse model of neurodegenerative metabolic disease. PLoS One. Dec 1 2010;5(12):e14192.
31. Delgadillo V, O'Callaghan Mdel M, Artuch R, Montero R, Pineda M. Genistein supplementation in patients affected by Sanfilippo disease. J. Inherit. Metab. Dis. Oct 2011;34(5):1039-1044.
32. Kim KH, Dodsworth C, Paras A, Burton BK. High dose genistein aglycone therapy is safe in patients with mucopolysaccharidoses involving the central nervous system. Mol. Genet. Metab. Aug 2013;109(4):382-385.
33. Matos L, Canals I, Dridi L, et al. Therapeutic strategies based on modified U1 snRNAs and chaperones for Sanfilippo C splicing mutations. Orphanet J. Rare Dis. Dec 10 2014;9:180.
34. Kan SH, Aoyagi-Scharber M, Le SQ, et al. Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB. Proc. Natl. Acad. Sci. U. S. A. Oct 14 2014;111(41):14870-14875.
35. Kan SH, Troitskaya LA, Sinow CS, et al. Insulin-like growth factor II peptide fusion enables uptake and lysosomal delivery of alpha-N-acetylglucosaminidase to mucopolysaccharidosis type IIIB fibroblasts. Biochem. J. Mar 01 2014;458(2):281-289.
36. Yogalingam G, Luu AR, Prill H, et al. BMN 250, a fusion of lysosomal alpha-N-acetylglucosaminidase with IGF2, exhibits different patterns of cellular uptake into critical cell types of Sanfilippo syndrome B disease pathogenesis. PLoS One. 2019;14(1):e0207836.
37. Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N. Engl. J. Med. Jan 18 2001;344(3):182-188.
38. Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol. Genet. Metab. Mar 2007;90(3):329-337.
39. Hendriksz CJ, Burton B, Fleming TR, et al. Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study. J. Inherit. Metab. Dis. Nov 2014;37(6):979-990.
40. Harmatz P, Giugliani R, Schwartz I, et al. 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. Apr 2006;148(4):533-539.
41. Fox JE, Volpe L, Bullaro J, Kakkis ED, Sly WS. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient. Mol. Genet. Metab. Feb 2015;114(2):203-208.
42. Boado RJ, Lu JZ, Hui EK, Pardridge WM. Insulin receptor antibody-sulfamidase fusion protein penetrates the primate blood-brain barrier and reduces glycosoaminoglycans in Sanfilippo type A cells. Mol. Pharm. Aug 4 2014;11(8):2928-2934.
43. Boado RJ, Ka-Wai Hui E, Zhiqiang Lu J, Pardridge WM. Insulin receptor antibody-iduronate 2-sulfatase fusion protein: pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys. Biotechnol. Bioeng. Nov 2014;111(11):2317-2325.
44. Boado RJ, Lu JZ, Hui EK, Lin H, Pardridge WM. Insulin Receptor Antibody-alpha-N-Acetylglucosaminidase Fusion Protein Penetrates the Primate Blood-Brain Barrier and Reduces Glycosoaminoglycans in Sanfilippo Type B Fibroblasts. Mol. Pharm. Apr 4 2016;13(4):1385-1392.
45. Boado RJ, Hui EK, Lu JZ, Pardridge WM. Very High Plasma Concentrations of a Monoclonal Antibody against the Human Insulin Receptor Are Produced by Subcutaneous Injection in the Rhesus Monkey. Mol. Pharm. Sep 6 2016;13(9):3241-3246.
46. Boado RJ, Lu JZ, Hui EK, Pardridge WM. Reduction in Brain Heparan Sulfate with Systemic Administration of an IgG Trojan Horse-Sulfamidase Fusion Protein in the Mucopolysaccharidosis Type IIIA Mouse. Mol. Pharm. Feb 5 2018;15(2):602-608.
47. King B, Marshall N, Beard H, et al. Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain. J. Inherit. Metab. Dis. Mar 2015;38(2):341-350.
48. Beard H, Luck AJ, Hassiotis S, et al. Determination of the role of injection site on the efficacy of intra-CSF enzyme replacement therapy in MPS IIIA mice. Mol. Genet. Metab. May 2015;115(1):33-40.
49. King B, Setford ML, Hassiotis S, et al. Low-dose, continual enzyme delivery ameliorates some aspects of established brain disease in a mouse model of a childhood-onset neurodegenerative disorder. Exp. Neurol. Apr 2016;278:11-21.
50. King B, Hassiotis S, Rozaklis T, et al. Low-dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA. J. Neurochem. May 2016;137(3):409-422.
51. Aoyagi-Scharber M, Crippen-Harmon D, Lawrence R, et al. Clearance of Heparan Sulfate and Attenuation of CNS Pathology by Intracerebroventricular BMN 250 in Sanfilippo Type B Mice. Molecular therapy. Methods & clinical development. Sep 15 2017;6:43-53.
52. Jones SA, Breen C, Heap F, et al. A phase 1/2 study of intrathecal heparan-N-sulfatase in patients with mucopolysaccharidosis IIIA. Mol. Genet. Metab. Jul 2016;118(3):198-205.
53. Wijburg FA, Whitley CB, Muenzer J, et al. Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial. Mol. Genet. Metab. Feb 2019;126(2):121-130.
54. Rutkowski JV, Harbert K, Xu H, et al. Intravenous SBC-103, a recombinant human alpha-N-acetylglucosaminidase reduces CNS heparan sulfate content in a mucopolysaccharidosis type IIIB mouse model. Mol. Genet. Metab. 2014/02/01/ 2014;111(2):S92.
55. Whitley CB, Vijay S, Yao B, et al. Final results of the phase 1/2, open-label clinical study of intravenous recombinant human N-acetyl-alpha-d-glucosaminidase (SBC-103) in children with mucopolysaccharidosis IIIB. Mol. Genet. Metab. Feb 2019;126(2):131-138.
56. Haurigot V, Marco S, Ribera A, et al. Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy. J. Clin. Invest. Aug 1 2013;123(8):3254-3271.
57. Hocquemiller M, Giersch L, Audrain M, Parker S, Cartier N. Adeno-Associated Virus-Based Gene Therapy for CNS Diseases. Hum. Gene Ther. Jul 2016;27(7):478-496.
58. Ribera A, Haurigot V, Garcia M, et al. Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy. Hum. Mol. Genet. Apr 01 2015;24(7):2078-2095.
59. Roca C, Motas S, Marco S, et al. Disease correction by AAV-mediated gene therapy in a new mouse model of mucopolysaccharidosis type IIID. Hum. Mol. Genet. Apr 15 2017;26(8):1535-1551.
60. Marco S, Haurigot V, Bosch F. In Vivo Gene Therapy for Mucopolysaccharidosis Type III (Sanfilippo Syndrome): A New Treatment Horizon. Hum. Gene Ther. Oct 2019;30(10):1211-1221.
61. Agbandje-McKenna M, Kuhn R. Current opinion in virology: structural virology. Curr. Opin. Virol. Aug 2011;1(2):81-83.
62. Mingozzi F, High KA. Immune responses to AAV in clinical trials. Curr. Gene Ther. Aug 2011;11(4):321-330.
63. Naldini L. Gene therapy returns to centre stage. Nature. Oct 15 2015;526(7573):351-360.
64. Buchlis G, Podsakoff GM, Radu A, et al. Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer. Blood. Mar 29 2012;119(13):3038-3041.
65. Hordeaux J, Hinderer C, Buza EL, et al. Safe and Sustained Expression of Human Iduronidase After Intrathecal Administration of Adeno-Associated Virus Serotype 9 in Infant Rhesus Monkeys. Hum. Gene Ther. Aug 2019;30(8):957-966.
66. Jaen ML, Vila L, Elias I, et al. Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs. Molecular therapy. Methods & clinical development. Sep 15 2017;6:1-7.
67. Leone P, Shera D, McPhee SW, et al. Long-term follow-up after gene therapy for canavan disease. Sci. Transl. Med. Dec 19 2012;4(165):165ra163.
68. Mittermeyer G, Christine CW, Rosenbluth KH, et al. Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease. Hum. Gene Ther. Apr 2012;23(4):377-381.
69. Sondhi D, Johnson L, Purpura K, et al. Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis. Human gene therapy methods. Oct 2012;23(5):324-335.
70. Gilkes JA, Bloom MD, Heldermon CD. Preferred transduction with AAV8 and AAV9 via thalamic administration in the MPS IIIB model: A comparison of four rAAV serotypes. Molecular genetics and metabolism reports. Mar 2016;6:48-54.
71. Fu H, Kang L, Jennings JS, et al. Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice. Gene Ther. Jul 2007;14(14):1065-1077.
72. Murrey DA, Naughton BJ, Duncan FJ, et al. Feasibility and safety of systemic rAAV9-hNAGLU delivery for treating mucopolysaccharidosis IIIB: toxicology, biodistribution, and immunological assessments in primates. Human gene therapy. Clinical development. Jun 2014;25(2):72-84.
73. Meadows AS, Duncan FJ, Camboni M, et al. A GLP-Compliant Toxicology and Biodistribution Study: Systemic Delivery of an rAAV9 Vector for the Treatment of Mucopolysaccharidosis IIIB. Human gene therapy. Clinical development. Dec 2015;26(4):228-242.
74. Winner LK, Beard H, Hassiotis S, et al. A Preclinical Study Evaluating AAVrh10-Based Gene Therapy for Sanfilippo Syndrome. Hum. Gene Ther. May 2016;27(5):363-375.
75. Falese L, Sandza K, Yates B, et al. Strategy to detect pre-existing immunity to AAV gene therapy. Gene Ther. Dec 2017;24(12):768-778.
76. Boutin S, Monteilhet V, Veron P, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum. Gene Ther. Jun 2010;21(6):704-712.
77. Calcedo R, Morizono H, Wang L, et al. Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clin. Vaccine Immunol. Sep 2011;18(9):1586-1588.
78. McIntyre C, Derrick-Roberts AL, Byers S, Anson DS. Correction of murine mucopolysaccharidosis type IIIA central nervous system pathology by intracerebroventricular lentiviral-mediated gene delivery. J. Gene Med. Nov-Dec 2014;16(11-12):374-387.
79. Heldermon CD, Qin EY, Ohlemiller KK, et al. Disease correction by combined neonatal intracranial AAV and systemic lentiviral gene therapy in Sanfilippo Syndrome type B mice. Gene Ther. Sep 2013;20(9):913-921.
80. Tardieu M, Zerah M, Husson B, et al. Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a phase I/II trial. Hum. Gene Ther. Jun 2014;25(6):506-516.
81. Tardieu M, Zerah M, Gougeon ML, et al. Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial. Lancet Neurol. Sep 2017;16(9):712-720.
82. Chen Y, Xu LP, Zhang XH, et al. Busulfan, Fludarabine, and Cyclophosphamide (BFC) conditioning allowed stable engraftment after haplo-identical allogeneic stem cell transplantation in children with adrenoleukodystrophy and mucopolysaccharidosis. Bone Marrow Transplant. Jun 2018;53(6):770-773.
83. Taylor M, Khan S, Stapleton M, et al. Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future. Biol. Blood Marrow Transplant. Jul 2019;25(7):e226-e246.
84. Tan EY, Boelens JJ, Jones SA, Wynn RF. Hematopoietic Stem Cell Transplantation in Inborn Errors of Metabolism. Frontiers in pediatrics. 2019;7:433.
85. Sivakumur P, Wraith JE. Bone marrow transplantation in mucopolysaccharidosis type IIIA: a comparison of an early treated patient with his untreated sibling. J. Inherit. Metab. Dis. Oct 1999;22(7):849-850.
86. Vellodi A, Young E, New M, Pot-Mees C, Hugh-Jones K. Bone marrow transplantation for Sanfilippo disease type B. J. Inherit. Metab. Dis. 1992;15(6):911-918.
87. Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. Mar 26 2015;125(13):2164-2172.
88. Prasad VK, Mendizabal A, Parikh SH, et al. Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes. Blood. Oct 1 2008;112(7):2979-2989.
89. Welling L, Marchal JP, van Hasselt P, van der Ploeg AT, Wijburg FA, Boelens JJ. Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III. JIMD reports. 2015;18:63-68.
90. Willing AE, Garbuzova-Davis SN, Zayko O, et al. Repeated administrations of human umbilical cord blood cells improve disease outcomes in a mouse model of Sanfilippo syndrome type III B. Cell Transplant. 2014;23(12):1613-1630.
91. Fraldi A, Serafini M, Sorrentino NC, Gentner B, Aiuti A, Bernardo ME. Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches. Ital. J. Pediatr. Nov 16 2018;44(Suppl 2):130.
92. Ellison SM, Liao A, Wood S, et al. Pre-clinical Safety and Efficacy of Lentiviral Vector-Mediated Ex Vivo Stem Cell Gene Therapy for the Treatment of Mucopolysaccharidosis IIIA. Molecular therapy. Methods & clinical development. Jun 14 2019;13:399-413.
93. Holley RJ, Ellison SM, Fil D, et al. Macrophage enzyme and reduced inflammation drive brain correction of mucopolysaccharidosis IIIB by stem cell gene therapy. Brain. Jan 1 2018;141(1):99-116.
94. Langford-Smith A, Wilkinson FL, Langford-Smith KJ, et al. Hematopoietic stem cell and gene therapy corrects primary neuropathology and behavior in mucopolysaccharidosis IIIA mice. Mol. Ther. Aug 2012;20(8):1610-1621.
95. Sergijenko A, Langford-Smith A, Liao AY, et al. Myeloid/Microglial driven autologous hematopoietic stem cell gene therapy corrects a neuronopathic lysosomal disease. Mol. Ther. Oct 2013;21(10):1938-1949.
96. Clarke D, Pearse Y, Kan SH, et al. Genetically Corrected iPSC-Derived Neural Stem Cell Grafts Deliver Enzyme Replacement to Affect CNS Disease in Sanfilippo B Mice. Molecular therapy. Methods & clinical development. Sep 21 2018;10:113-127.
97. Espuny-Camacho I, Arranz AM, Fiers M, et al. Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain. Neuron. Mar 8 2017;93(5):1066-1081 e1068.
98. Griffin TA, Anderson HC, Wolfe JH. Ex vivo gene therapy using patient iPSC-derived NSCs reverses pathology in the brain of a homologous mouse model. Stem cell reports. May 12 2015;4(5):835-846.
99. McGinley LM, Kashlan ON, Bruno ES, et al. Human neural stem cell transplantation improves cognition in a murine model of Alzheimer's disease. Sci. Rep. Oct 3 2018;8(1):14776.
100. Snyder EY, Taylor RM, Wolfe JH. Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. Nature. Mar 23 1995;374(6520):367-370.
101. Zhang T, Ke W, Zhou X, et al. Human Neural Stem Cells Reinforce Hippocampal Synaptic Network and Rescue Cognitive Deficits in a Mouse Model of Alzheimer's Disease. Stem cell reports.
2. Fedele AO. Sanfilippo syndrome: causes, consequences, and treatments. The application of clinical genetics. 2015;8:269-281.
3. Jakobkiewicz-Banecka J, Gabig-Ciminska M, Kloska A, et al. Glycosaminoglycans and mucopolysaccharidosis type III. Frontiers in bioscience (Landmark edition). Jun 1 2016;21:1393-1409.
4. Kresse H, Neufeld EF. The Sanfilippo A corrective factor. Purification and mode of action. J. Biol. Chem. Apr 10 1972;247(7):2164-2170.
5. von Figura K. Human alpha-n-acetylglucosaminidase. 2. Activity towards natural substrates and multiple recognition forms. Eur. J. Biochem. Nov 1 1977;80(2):535-542.
6. Klein U, Kresse H, von Figura K. Sanfilippo syndrome type C: deficiency of acetyl-CoA:alpha-glucosaminide N-acetyltransferase in skin fibroblasts. Proc. Natl. Acad. Sci. U. S. A. Oct 1978;75(10):5185-5189.
7. Kowalewski B, Lamanna WC, Lawrence R, et al. Arylsulfatase G inactivation causes loss of heparan sulfate 3-O-sulfatase activity and mucopolysaccharidosis in mice. Proc. Natl. Acad. Sci. U. S. A. Jun 26 2012;109(26):10310-10315.
8. Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA. Sanfilippo syndrome: a mini-review. J. Inherit. Metab. Dis. Apr 2008;31(2):240-252.
9. Cross EM, Hare DJ. Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders. J. Inherit. Metab. Dis. Mar 2013;36(2):189-200.
10. Lyon GK, E.H. Pastores, G.M. Neurology of Hereditary Metabolic Diseases of Children. 3 ed. New York: Mc Graw Hill; 2006.
11. Wraith JE. Mucopolysaccharidoses and Oligosaccharidoses. In: Fernandes J, Saudubray J-M, van den Berghe G, Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. Berlin, Heidelberg: Springer Berlin Heidelberg; 2006:495-507.
12. Giugliani R, Federhen A, Vairo F, et al. Emerging drugs for the treatment of mucopolysaccharidoses. Expert opinion on emerging drugs. 2016;21(1):9-26.
13. Gaffke L, Pierzynowska K, Piotrowska E, Wegrzyn G. How close are we to therapies for Sanfilippo disease? Metab. Brain Dis. Feb 2018;33(1):1-10.
14. Lancaster MA, Knoblich JA. Generation of cerebral organoids from human pluripotent stem cells. Nat. Protoc. Oct 2014;9(10):2329-2340.
15. Allende ML, Cook EK, Larman BC, et al. Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation. J. Lipid Res. Mar 2018;59(3):550-563.
16. Camp JG, Badsha F, Florio M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl. Acad. Sci. U. S. A. Dec 22 2015;112(51):15672-15677.
17. Cederquist GY, Asciolla JJ, Tchieu J, et al. Specification of positional identity in forebrain organoids. Nat. Biotechnol. Apr 2019;37(4):436-444.
18. Choi SH, Kim YH, Hebisch M, et al. A three-dimensional human neural cell culture model of Alzheimer's disease. Nature. Nov 13 2014;515(7526):274-278.
19. Jo J, Xiao Y, Sun AX, et al. Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons. Cell stem cell. Aug 4 2016;19(2):248-257.
20. Vallejo S, Fleischer A, Martin JM, Sanchez A, Palomino E, Bachiller D. Generation of two induced pluripotent stem cells lines from Mucopolysaccharydosis IIIA patient: IMEDEAi004-A and IMEDEAi004-B. Stem cell research. Oct 2018;32:110-114.
21. Vallejo-Diez S, Fleischer A, Martin-Fernandez JM, Sanchez-Gilabert A, Bachiller D. Generation of two induced pluripotent stem cells lines from a Mucopolysaccharydosis IIIB (MPSIIIB) patient. Stem cell research. Dec 2018;33:180-184.
22. Ghosh A, Shapiro E, Rust S, et al. Recommendations on clinical trial design for treatment of Mucopolysaccharidosis Type III. Orphanet J. Rare Dis. Jun 26 2017;12(1):117.
23. Platt FM, Butters TD. Substrate Reduction Therapy. Lysosomal Storage Disorders. Boston, MA: Springer US; 2007:153-168.
24. Dziedzic D, Wegrzyn G, Jakobkiewicz-Banecka J. Impairment of glycosaminoglycan synthesis in mucopolysaccharidosis type IIIA cells by using siRNA: a potential therapeutic approach for Sanfilippo disease. Eur. J. Hum. Genet. Feb 2010;18(2):200-205.
25. Kaidonis X, Liaw WC, Roberts AD, Ly M, Anson D, Byers S. Gene silencing of EXTL2 and EXTL3 as a substrate deprivation therapy for heparan sulphate storing mucopolysaccharidoses. Eur. J. Hum. Genet. Feb 2010;18(2):194-199.
26. Canals I, Beneto N, Cozar M, Vilageliu L, Grinberg D. EXTL2 and EXTL3 inhibition with siRNAs as a promising substrate reduction therapy for Sanfilippo C syndrome. Sci. Rep. Sep 8 2015;5:13654.
27. Pisano MM, Greene RM. Epidermal growth factor potentiates the induction of ornithine decarboxylase activity by prostaglandins in embryonic palate mesenchymal cells: effects on cell proliferation and glycosaminoglycan synthesis. Dev. Biol. Aug 1987;122(2):419-431.
28. Tirone E, D'Alessandris C, Hascall VC, Siracusa G, Salustri A. Hyaluronan synthesis by mouse cumulus cells is regulated by interactions between follicle-stimulating hormone (or epidermal growth factor) and a soluble oocyte factor (or transforming growth factor beta1). J. Biol. Chem. Feb 21 1997;272(8):4787-4794.
29. Jakobkiewicz-Banecka J, Piotrowska E, Narajczyk M, Baranska S, Wegrzyn G. Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway. J. Biomed. Sci. Mar 2 2009;16:26.
30. Malinowska M, Wilkinson FL, Langford-Smith KJ, et al. Genistein improves neuropathology and corrects behaviour in a mouse model of neurodegenerative metabolic disease. PLoS One. Dec 1 2010;5(12):e14192.
31. Delgadillo V, O'Callaghan Mdel M, Artuch R, Montero R, Pineda M. Genistein supplementation in patients affected by Sanfilippo disease. J. Inherit. Metab. Dis. Oct 2011;34(5):1039-1044.
32. Kim KH, Dodsworth C, Paras A, Burton BK. High dose genistein aglycone therapy is safe in patients with mucopolysaccharidoses involving the central nervous system. Mol. Genet. Metab. Aug 2013;109(4):382-385.
33. Matos L, Canals I, Dridi L, et al. Therapeutic strategies based on modified U1 snRNAs and chaperones for Sanfilippo C splicing mutations. Orphanet J. Rare Dis. Dec 10 2014;9:180.
34. Kan SH, Aoyagi-Scharber M, Le SQ, et al. Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB. Proc. Natl. Acad. Sci. U. S. A. Oct 14 2014;111(41):14870-14875.
35. Kan SH, Troitskaya LA, Sinow CS, et al. Insulin-like growth factor II peptide fusion enables uptake and lysosomal delivery of alpha-N-acetylglucosaminidase to mucopolysaccharidosis type IIIB fibroblasts. Biochem. J. Mar 01 2014;458(2):281-289.
36. Yogalingam G, Luu AR, Prill H, et al. BMN 250, a fusion of lysosomal alpha-N-acetylglucosaminidase with IGF2, exhibits different patterns of cellular uptake into critical cell types of Sanfilippo syndrome B disease pathogenesis. PLoS One. 2019;14(1):e0207836.
37. Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N. Engl. J. Med. Jan 18 2001;344(3):182-188.
38. Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol. Genet. Metab. Mar 2007;90(3):329-337.
39. Hendriksz CJ, Burton B, Fleming TR, et al. Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study. J. Inherit. Metab. Dis. Nov 2014;37(6):979-990.
40. Harmatz P, Giugliani R, Schwartz I, et al. 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. Apr 2006;148(4):533-539.
41. Fox JE, Volpe L, Bullaro J, Kakkis ED, Sly WS. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient. Mol. Genet. Metab. Feb 2015;114(2):203-208.
42. Boado RJ, Lu JZ, Hui EK, Pardridge WM. Insulin receptor antibody-sulfamidase fusion protein penetrates the primate blood-brain barrier and reduces glycosoaminoglycans in Sanfilippo type A cells. Mol. Pharm. Aug 4 2014;11(8):2928-2934.
43. Boado RJ, Ka-Wai Hui E, Zhiqiang Lu J, Pardridge WM. Insulin receptor antibody-iduronate 2-sulfatase fusion protein: pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys. Biotechnol. Bioeng. Nov 2014;111(11):2317-2325.
44. Boado RJ, Lu JZ, Hui EK, Lin H, Pardridge WM. Insulin Receptor Antibody-alpha-N-Acetylglucosaminidase Fusion Protein Penetrates the Primate Blood-Brain Barrier and Reduces Glycosoaminoglycans in Sanfilippo Type B Fibroblasts. Mol. Pharm. Apr 4 2016;13(4):1385-1392.
45. Boado RJ, Hui EK, Lu JZ, Pardridge WM. Very High Plasma Concentrations of a Monoclonal Antibody against the Human Insulin Receptor Are Produced by Subcutaneous Injection in the Rhesus Monkey. Mol. Pharm. Sep 6 2016;13(9):3241-3246.
46. Boado RJ, Lu JZ, Hui EK, Pardridge WM. Reduction in Brain Heparan Sulfate with Systemic Administration of an IgG Trojan Horse-Sulfamidase Fusion Protein in the Mucopolysaccharidosis Type IIIA Mouse. Mol. Pharm. Feb 5 2018;15(2):602-608.
47. King B, Marshall N, Beard H, et al. Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain. J. Inherit. Metab. Dis. Mar 2015;38(2):341-350.
48. Beard H, Luck AJ, Hassiotis S, et al. Determination of the role of injection site on the efficacy of intra-CSF enzyme replacement therapy in MPS IIIA mice. Mol. Genet. Metab. May 2015;115(1):33-40.
49. King B, Setford ML, Hassiotis S, et al. Low-dose, continual enzyme delivery ameliorates some aspects of established brain disease in a mouse model of a childhood-onset neurodegenerative disorder. Exp. Neurol. Apr 2016;278:11-21.
50. King B, Hassiotis S, Rozaklis T, et al. Low-dose, continuous enzyme replacement therapy ameliorates brain pathology in the neurodegenerative lysosomal disorder mucopolysaccharidosis type IIIA. J. Neurochem. May 2016;137(3):409-422.
51. Aoyagi-Scharber M, Crippen-Harmon D, Lawrence R, et al. Clearance of Heparan Sulfate and Attenuation of CNS Pathology by Intracerebroventricular BMN 250 in Sanfilippo Type B Mice. Molecular therapy. Methods & clinical development. Sep 15 2017;6:43-53.
52. Jones SA, Breen C, Heap F, et al. A phase 1/2 study of intrathecal heparan-N-sulfatase in patients with mucopolysaccharidosis IIIA. Mol. Genet. Metab. Jul 2016;118(3):198-205.
53. Wijburg FA, Whitley CB, Muenzer J, et al. Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial. Mol. Genet. Metab. Feb 2019;126(2):121-130.
54. Rutkowski JV, Harbert K, Xu H, et al. Intravenous SBC-103, a recombinant human alpha-N-acetylglucosaminidase reduces CNS heparan sulfate content in a mucopolysaccharidosis type IIIB mouse model. Mol. Genet. Metab. 2014/02/01/ 2014;111(2):S92.
55. Whitley CB, Vijay S, Yao B, et al. Final results of the phase 1/2, open-label clinical study of intravenous recombinant human N-acetyl-alpha-d-glucosaminidase (SBC-103) in children with mucopolysaccharidosis IIIB. Mol. Genet. Metab. Feb 2019;126(2):131-138.
56. Haurigot V, Marco S, Ribera A, et al. Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy. J. Clin. Invest. Aug 1 2013;123(8):3254-3271.
57. Hocquemiller M, Giersch L, Audrain M, Parker S, Cartier N. Adeno-Associated Virus-Based Gene Therapy for CNS Diseases. Hum. Gene Ther. Jul 2016;27(7):478-496.
58. Ribera A, Haurigot V, Garcia M, et al. Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy. Hum. Mol. Genet. Apr 01 2015;24(7):2078-2095.
59. Roca C, Motas S, Marco S, et al. Disease correction by AAV-mediated gene therapy in a new mouse model of mucopolysaccharidosis type IIID. Hum. Mol. Genet. Apr 15 2017;26(8):1535-1551.
60. Marco S, Haurigot V, Bosch F. In Vivo Gene Therapy for Mucopolysaccharidosis Type III (Sanfilippo Syndrome): A New Treatment Horizon. Hum. Gene Ther. Oct 2019;30(10):1211-1221.
61. Agbandje-McKenna M, Kuhn R. Current opinion in virology: structural virology. Curr. Opin. Virol. Aug 2011;1(2):81-83.
62. Mingozzi F, High KA. Immune responses to AAV in clinical trials. Curr. Gene Ther. Aug 2011;11(4):321-330.
63. Naldini L. Gene therapy returns to centre stage. Nature. Oct 15 2015;526(7573):351-360.
64. Buchlis G, Podsakoff GM, Radu A, et al. Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer. Blood. Mar 29 2012;119(13):3038-3041.
65. Hordeaux J, Hinderer C, Buza EL, et al. Safe and Sustained Expression of Human Iduronidase After Intrathecal Administration of Adeno-Associated Virus Serotype 9 in Infant Rhesus Monkeys. Hum. Gene Ther. Aug 2019;30(8):957-966.
66. Jaen ML, Vila L, Elias I, et al. Long-Term Efficacy and Safety of Insulin and Glucokinase Gene Therapy for Diabetes: 8-Year Follow-Up in Dogs. Molecular therapy. Methods & clinical development. Sep 15 2017;6:1-7.
67. Leone P, Shera D, McPhee SW, et al. Long-term follow-up after gene therapy for canavan disease. Sci. Transl. Med. Dec 19 2012;4(165):165ra163.
68. Mittermeyer G, Christine CW, Rosenbluth KH, et al. Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease. Hum. Gene Ther. Apr 2012;23(4):377-381.
69. Sondhi D, Johnson L, Purpura K, et al. Long-term expression and safety of administration of AAVrh.10hCLN2 to the brain of rats and nonhuman primates for the treatment of late infantile neuronal ceroid lipofuscinosis. Human gene therapy methods. Oct 2012;23(5):324-335.
70. Gilkes JA, Bloom MD, Heldermon CD. Preferred transduction with AAV8 and AAV9 via thalamic administration in the MPS IIIB model: A comparison of four rAAV serotypes. Molecular genetics and metabolism reports. Mar 2016;6:48-54.
71. Fu H, Kang L, Jennings JS, et al. Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice. Gene Ther. Jul 2007;14(14):1065-1077.
72. Murrey DA, Naughton BJ, Duncan FJ, et al. Feasibility and safety of systemic rAAV9-hNAGLU delivery for treating mucopolysaccharidosis IIIB: toxicology, biodistribution, and immunological assessments in primates. Human gene therapy. Clinical development. Jun 2014;25(2):72-84.
73. Meadows AS, Duncan FJ, Camboni M, et al. A GLP-Compliant Toxicology and Biodistribution Study: Systemic Delivery of an rAAV9 Vector for the Treatment of Mucopolysaccharidosis IIIB. Human gene therapy. Clinical development. Dec 2015;26(4):228-242.
74. Winner LK, Beard H, Hassiotis S, et al. A Preclinical Study Evaluating AAVrh10-Based Gene Therapy for Sanfilippo Syndrome. Hum. Gene Ther. May 2016;27(5):363-375.
75. Falese L, Sandza K, Yates B, et al. Strategy to detect pre-existing immunity to AAV gene therapy. Gene Ther. Dec 2017;24(12):768-778.
76. Boutin S, Monteilhet V, Veron P, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum. Gene Ther. Jun 2010;21(6):704-712.
77. Calcedo R, Morizono H, Wang L, et al. Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clin. Vaccine Immunol. Sep 2011;18(9):1586-1588.
78. McIntyre C, Derrick-Roberts AL, Byers S, Anson DS. Correction of murine mucopolysaccharidosis type IIIA central nervous system pathology by intracerebroventricular lentiviral-mediated gene delivery. J. Gene Med. Nov-Dec 2014;16(11-12):374-387.
79. Heldermon CD, Qin EY, Ohlemiller KK, et al. Disease correction by combined neonatal intracranial AAV and systemic lentiviral gene therapy in Sanfilippo Syndrome type B mice. Gene Ther. Sep 2013;20(9):913-921.
80. Tardieu M, Zerah M, Husson B, et al. Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a phase I/II trial. Hum. Gene Ther. Jun 2014;25(6):506-516.
81. Tardieu M, Zerah M, Gougeon ML, et al. Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial. Lancet Neurol. Sep 2017;16(9):712-720.
82. Chen Y, Xu LP, Zhang XH, et al. Busulfan, Fludarabine, and Cyclophosphamide (BFC) conditioning allowed stable engraftment after haplo-identical allogeneic stem cell transplantation in children with adrenoleukodystrophy and mucopolysaccharidosis. Bone Marrow Transplant. Jun 2018;53(6):770-773.
83. Taylor M, Khan S, Stapleton M, et al. Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future. Biol. Blood Marrow Transplant. Jul 2019;25(7):e226-e246.
84. Tan EY, Boelens JJ, Jones SA, Wynn RF. Hematopoietic Stem Cell Transplantation in Inborn Errors of Metabolism. Frontiers in pediatrics. 2019;7:433.
85. Sivakumur P, Wraith JE. Bone marrow transplantation in mucopolysaccharidosis type IIIA: a comparison of an early treated patient with his untreated sibling. J. Inherit. Metab. Dis. Oct 1999;22(7):849-850.
86. Vellodi A, Young E, New M, Pot-Mees C, Hugh-Jones K. Bone marrow transplantation for Sanfilippo disease type B. J. Inherit. Metab. Dis. 1992;15(6):911-918.
87. Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. Mar 26 2015;125(13):2164-2172.
88. Prasad VK, Mendizabal A, Parikh SH, et al. Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes. Blood. Oct 1 2008;112(7):2979-2989.
89. Welling L, Marchal JP, van Hasselt P, van der Ploeg AT, Wijburg FA, Boelens JJ. Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III. JIMD reports. 2015;18:63-68.
90. Willing AE, Garbuzova-Davis SN, Zayko O, et al. Repeated administrations of human umbilical cord blood cells improve disease outcomes in a mouse model of Sanfilippo syndrome type III B. Cell Transplant. 2014;23(12):1613-1630.
91. Fraldi A, Serafini M, Sorrentino NC, Gentner B, Aiuti A, Bernardo ME. Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches. Ital. J. Pediatr. Nov 16 2018;44(Suppl 2):130.
92. Ellison SM, Liao A, Wood S, et al. Pre-clinical Safety and Efficacy of Lentiviral Vector-Mediated Ex Vivo Stem Cell Gene Therapy for the Treatment of Mucopolysaccharidosis IIIA. Molecular therapy. Methods & clinical development. Jun 14 2019;13:399-413.
93. Holley RJ, Ellison SM, Fil D, et al. Macrophage enzyme and reduced inflammation drive brain correction of mucopolysaccharidosis IIIB by stem cell gene therapy. Brain. Jan 1 2018;141(1):99-116.
94. Langford-Smith A, Wilkinson FL, Langford-Smith KJ, et al. Hematopoietic stem cell and gene therapy corrects primary neuropathology and behavior in mucopolysaccharidosis IIIA mice. Mol. Ther. Aug 2012;20(8):1610-1621.
95. Sergijenko A, Langford-Smith A, Liao AY, et al. Myeloid/Microglial driven autologous hematopoietic stem cell gene therapy corrects a neuronopathic lysosomal disease. Mol. Ther. Oct 2013;21(10):1938-1949.
96. Clarke D, Pearse Y, Kan SH, et al. Genetically Corrected iPSC-Derived Neural Stem Cell Grafts Deliver Enzyme Replacement to Affect CNS Disease in Sanfilippo B Mice. Molecular therapy. Methods & clinical development. Sep 21 2018;10:113-127.
97. Espuny-Camacho I, Arranz AM, Fiers M, et al. Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain. Neuron. Mar 8 2017;93(5):1066-1081 e1068.
98. Griffin TA, Anderson HC, Wolfe JH. Ex vivo gene therapy using patient iPSC-derived NSCs reverses pathology in the brain of a homologous mouse model. Stem cell reports. May 12 2015;4(5):835-846.
99. McGinley LM, Kashlan ON, Bruno ES, et al. Human neural stem cell transplantation improves cognition in a murine model of Alzheimer's disease. Sci. Rep. Oct 3 2018;8(1):14776.
100. Snyder EY, Taylor RM, Wolfe JH. Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. Nature. Mar 23 1995;374(6520):367-370.
101. Zhang T, Ke W, Zhou X, et al. Human Neural Stem Cells Reinforce Hippocampal Synaptic Network and Rescue Cognitive Deficits in a Mouse Model of Alzheimer's Disease. Stem cell reports.