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http://dx.doi.org/10.19125/jmrd.2021.5.1.22

Novel Therapeutic Approaches to Mucopolysaccharidosis Type III  

Yang, Aram (Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine)
Publication Information
Journal of mucopolysaccharidosis and rare diseases / v.5, no.1, 2021 , pp. 22-28 More about this Journal
Abstract
Mucopolysaccharidosis type III (MPS III) or Sanfilippo disease is an orphan-inherited lysosomal storage disease. It is one of the most common MPS subtypes. The classical presentation is an infantile-onset neurodegenerative disease characterized by intellectual regression, behavioral and sleep disturbances, loss of ambulation, and early death. Unlike other MPS, no disease-modifying therapy has been approved. Here, we review the curative therapy developed for MPS III, from historically ineffective hematopoietic stem cell transplantation and substrate reduction therapy to the promising enzyme replacement therapy or adeno-associated/lentiviral vector-mediated gene therapy. Preclinical studies are presented with recent translational first-in-man trials. We also present experimental research with preclinical mRNA and gene-editing strategies. Lessons from animal studies and clinical trials have highlighted the importance of early therapy before extensive neuronal loss. Disease-modifying therapy for MPS III will likely mandate the development of new early diagnosis strategies.
Keywords
Mucopolysaccharidosis type III; Sanfilippo disease; Lysosomal storage disease; Heparin sulfate; Gene therapy; Substrate reduction therapy;
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1 Weber B, Hopwood JJ, Yogalingam G. Expression and characterization of human recombinant and α-Nactylglucosaminidase. Protein expression and purification 2001;21:251-9.   DOI
2 Zhao K-W, Neufeld EF. Purification and characterization of recombinant human α-N-acetylglucosaminidase secreted by Chinese hamster ovary cells. Protein expression and purification 2000;19:202-11.   DOI
3 Kan S-h, Troitskaya LA, Sinow CS, Haitz K, Todd AK, Di Stefano A, et al. Insulin-like growth factor II peptide fusion enables uptake and lysosomal delivery of α-Nacetylglucosaminidase to mucopolysaccharidosis type IIIB fibroblasts. Biochemical Journal 2014;458:281-9.   DOI
4 Yogalingam G, Luu AR, Prill H, Lo MJ, Yip B, Holtzinger J, 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:e0207836.   DOI
5 Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebocontrolled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr 2004;144:581-8.   DOI
6 Muenzer J, Bodamer O, Burton B, Clarke L, Frenking GS, Giugliani R, et al. The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. European journal of pediatrics 2012;171:181-8.   DOI
7 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). Genetics in Medicine 2006;8:465-73.   DOI
8 Gaffke L, Pierzynowska K, Piotrowska E, Wegrzyn G. How close are we to therapies for Sanfilippo disease? Metabolic brain disease 2018;33:1-10.   DOI
9 Roberts AL, Thomas BJ, Wilkinson AS, Fletcher JM, Byers S. Inhibition of glycosaminoglycan synthesis using rhodamine B in a mouse model of mucopolysaccharidosis type IIIA. Pediatric research 2006;60:309-14.   DOI
10 Shapiro EG, Nestrasil I, Delaney KA, Rudser K, Kovac V, Nair N, et al. A Prospective Natural History Study of Mucopolysaccharidosis Type IIIA. J Pediatr 2016;170:278-87.e1-4.   DOI
11 Hemsley KM, King B, Hopwood JJ. Injection of recombinant human sulfamidase into the CSF via the cerebellomedullary cistern in MPS IIIA mice. Molecular genetics and metabolism 2007;90:313-28.   DOI
12 Beard H, Luck AJ, Hassiotis S, King B, Trim PJ, Snel MF, et al. Determination of the role of injection site on the efficacy of intra-CSF enzyme replacement therapy in MPS IIIA mice. Molecular genetics and metabolism 2015;115:33-40.   DOI
13 Pfeifer RW, Felice BR, Boyd RB, Butt MT, Ruiz JA, Heartlein MW, et al. Safety evaluation of chronic intrathecal administration of heparan N-sulfatase in juvenile cynomolgus monkeys. Drug delivery and translational research 2012;2:187-200.   DOI
14 Jones SA, Breen C, Heap F, Rust S, de Ruijter J, Tump E, et al. A phase 1/2 study of intrathecal heparan-N-sulfatase in patients with mucopolysaccharidosis IIIA. Molecular genetics and metabolism 2016;118:198-205.   DOI
15 Wijburg FA, Whitley CB, Muenzer J, Gasperini S, Del Toro M, Muschol N, et al. Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial. Molecular genetics and metabolism 2019;126:121-30.   DOI
16 Piotrowska E, Jakobkiewicz-Banecka J, Tylki-Szymanska A, Liberek A, Maryniak A, Malinowska M, et al. Genistin-rich soy isoflavone extract in substrate reduction therapy for Sanfilippo syndrome: An open-label, pilot study in 10 pediatric patients. Current therapeutic research 2008;69:166-79.   DOI
17 Suzuki Y. Emerging novel concept of chaperone therapies for protein misfolding diseases. Proceedings of the Japan Academy, Series B 2014;90:145-62.   DOI
18 de Ruijter J, Valstar MJ, Narajczyk M, Wegrzyn G, Kulik W, IJlst L, et al. Genistein in Sanfilippo disease: a randomized controlled crossover trial. Annals of neurology 2012;71:110-20.   DOI
19 Bernier V, Bichet DG, Bouvier M. Pharmacological chaperone action on G-protein-coupled receptors. Current opinion in pharmacology 2004;4:528-33.   DOI
20 King B, Marshall NR, Hassiotis S, Trim PJ, Tucker J, Hattersley K, et al. Slow, continuous enzyme replacement via spinal CSF in dogs with the paediatric-onset neurodegenerative disease, MPS IIIA. Journal of inherited metabolic disease 2017;40:443-53.   DOI
21 Matos L, Canals I, Dridi L, Choi Y, Prata MJ, Jordan P, et al. Therapeutic strategies based on modified U1 snRNAs and chaperones for Sanfilippo C splicing mutations. Orphanet J Rare Dis 2014;9:1-12.   DOI
22 Tardieu M, Zerah M, Husson B, de Bournonville S, Deiva K, Adamsbaum C, et al. Intracerebral administration of adenoassociated 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. Human gene therapy 2014;25:506-16.   DOI
23 Parenti G, Andria G, Valenzano KJ. Pharmacological chaperone therapy: preclinical development, clinical translation, and prospects for the treatment of lysosomal storage disorders. Molecular Therapy 2015;23:1138-48.   DOI
24 King B, Marshall N, Beard H, Hassiotis S, Trim PJ, Snel MF, et al. Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain. Journal of inherited metabolic disease 2015;38:341-50.   DOI
25 Fecarotta S, Gasperini S, Parenti G. New treatments for the mucopolysaccharidoses: from pathophysiology to therapy. Italian journal of pediatrics 2018;44:135-43.   DOI
26 Flanigan K, Simmons T, Mcbride K, Kunkler K, Alyward S, Couce M, et al. Phase 1/2 clinical trial of systemic gene transfer of scAAV9. U1a. hSGSH for MPS IIIA demonstrates 2 years of safety, tolerability, and biopotency. Molecular Genetics and Metabolism 2019;126:S54.
27 Tardieu M, Zerah M, Gougeon ML, Ausseil J, de Bournonville S, Husson B, et al. Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial. Lancet Neurol 2017;16:712-20.   DOI
28 McBride KL, Smith N, Couce M, Flanigan K, Truxal K, Simmons T, et al. Safety, Tolerability, and Preliminary Evidence of Biopotency in Transpher B, a Multicenter, Singledose, Phase 1/2 Clinical Trial of ABO-101 Gene Therapy for Sanfilippo Syndrome Type B (Mucopolysaccharidosis IIIB) (5175). AAN Enterprises; 2020.
29 Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA. Sanfilippo syndrome: a mini-review. J Inherit Metab Dis 2008;31:240-52.   DOI
30 Valstar MJ, Marchal JP, Grootenhuis M, Colland V, Wijburg FA. Cognitive development in patients with Mucopolysaccharidosis type III (Sanfilippo syndrome). Orphanet J Rare Dis 2011;6:43.   DOI
31 Platt FM, Butters TD. Substrate reduction therapy. Lysosomal storage disorders 2007:153-68.
32 Coutinho MF, Santos JI, Alves S. Less is more: substrate reduction therapy for lysosomal storage disorders. International journal of molecular sciences 2016;17:1065.   DOI
33 Kaji T, Kawashima T, Sakamoto M. Rhodamine B inhibition of glycosaminoglycan production by cultured human lip fibroblasts. Toxicology and applied pharmacology 1991;111:82-9.   DOI
34 Pardridge WM. CNS drug design based on principles of blood-brain barrier transport. Journal of neurochemistry 1998;70:1781-92.   DOI
35 Nainggolan-Sihombing G. The toxic effect of rhodamine B in rats. Paediatr Indones 1984;24:125-38.
36 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. Journal of biomedical science 2009;16:1-9.   DOI
37 Tsai T-H. Concurrent measurement of unbound genistein in the blood, brain and bile of anesthetized rats using microdialysis and its pharmacokinetic application. Journal of Chromatography A 2005;1073:317-22.   DOI
38 Malinowska M, Wilkinson FL, Bennett W, Langford-Smith KJ, O'Leary HA, Jakobkiewicz-Banecka J, et al. Genistein reduces lysosomal storage in peripheral tissues of mucopolysaccharide IIIB mice. Molecular genetics and metabolism 2009;98:235-42.   DOI
39 Malinowska M, Wilkinson FL, Langford-Smith KJ, Langford-Smith A, Brown JR, Crawford BE, et al. Genistein improves neuropathology and corrects behaviour in a mouse model of neurodegenerative metabolic disease. PloS one 2010;5:e14192.   DOI
40 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. Molecular genetics and metabolism 2015;114:203-8.   DOI
41 Piotrowska E, Jakobkiewicz-Banecka J, Baranska S, TylkiSzymanska A, Czartoryska B, Wegrzyn A, et al. Genisteinmediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. European Journal of Human Genetics 2006;14:846-52.   DOI
42 Feldhammer M, Durand S, Pshezhetsky AV. Protein misfolding as an underlying molecular defect in mucopolysaccharidosis III type C. PloS one 2009;4:e7434.   DOI
43 Broijersen A, Dalen P, Ezgu F, Huledal G, Lindqvist D, Wiken M, et al. Safety and tolerability of SOBI003 in pediatric MPS IIIA patients key study design features of the ongoing first-in-human study. 2019.
44 Concolino D, Deodato F, Parini R. Enzyme replacement therapy: efficacy and limitations. Italian Journal of Pediatrics 2018;44:120.   DOI