Details of Disease

General Information of Disease (ID: DISB083T)

• Disease Name: Mucopolysaccharidosis
• Synonyms: MPS; Mucopolysaccharidoses; mucopolysaccharidoses; mucopolysaccharidosis
• Disease Class: 5C56: Lysosomal disease
• Definition: A group of autosomal recessive or X-linked inherited lysosomal storage disorders affecting the metabolism of mucopolysaccharides, resulting in the accumulation of mucopolysaccharides in the body. Signs and symptoms include organomegaly, mental retardation, abnormal skeletal development, heart disorders, hearing loss, and central nervous system deficiencies.
• Disease Hierarchy:
  DIS9HKVW: Mucopolysaccharidosis or mucopolysaccharidosis-like disorder
  DISMFQKM: Developmental anomaly of metabolic origin
  DISV24X3: Carbohydrate metabolism disorder
  DIS6QM6U: Lysosomal storage disease
  DISB083T: Mucopolysaccharidosis
• ICD Code:
  ICD-11: ICD-11: 5C56.3
  ICD-9: ICD-9: 277.5
  Expand ICD-9: 277.5
• Disease Identifiers:
  MONDO ID: MONDO_0019249
  MESH ID: D009083
  UMLS CUI: C0026703
  MedGen ID: 7733
  Orphanet ID: 79213
  SNOMED CT ID: 11380006

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Elosulfase alfa	DMA9REV	Approved	NA	[1]
Galsulfase	DMER9YA	Approved	NA	[2]
Laronidase	DMYZ08N	Approved	NA	[3]
Vestronidase alfa	DM4UHZF	Approved	NA	[4]

This Disease is Treated as An Indication in 11 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Ataluren	DM4GXW3	Phase 3	Small molecular drug	[5]
UX-003	DM8LWPR	Phase 3	NA	[5]
LYS-SAF302	DMUQWRD	Phase 2/3	Gene therapy	[6]
ABO-101	DMUBLC3	Phase 1/2	Gene therapy	[7]
ABO-102	DMFJB35	Phase 1/2	Gene therapy	[8]
AGT-181	DMKN3SA	Phase 1/2	NA	[5]
RGX-121	DMU3PD7	Phase 1/2	Gene therapy	[9]
SB-318	DMA8Z4N	Phase 1/2	Gene therapy	[10]
SB-913	DM98YFK	Phase 1/2	Gene therapy	[11]
SBC-103	DMMMK3F	Phase 1/2	NA	[5]
RGX-111	DMU87HW	Phase 1	Gene therapy	[12]

This Disease is Treated as An Indication in 2 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Gene therapy, mucopolysaccharidosis type I	DMODVYR	Investigative	NA	[13]
ZP-10719	DML5AYX	Investigative	NA	[13]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ARSB	TTESQTG	Strong	Genetic Variation	[14]
DPEP1	TTYUENF	Strong	Genetic Variation	[15]
GALNS	TTT9YPO	Strong	Genetic Variation	[16]
IDUA	TT0IUKX	Strong	Genetic Variation	[17]
NAGLU	TTDM6HZ	Strong	Altered Expression	[18]
SGSH	TTPJ2SH	Strong	Biomarker	[19]
TTK	TTP7EGM	Strong	Genetic Variation	[20]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ALAS2	DE437BY	Strong	Altered Expression	[21]

This Disease Is Related to 15 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
EXTL2	OT8U672K	Limited	Biomarker	[22]
EXTL3	OT2BRUBN	Limited	Biomarker	[22]
GNS	OTNFKYGB	Limited	Genetic Variation	[23]
HGSNAT	OTXPCELL	Limited	Genetic Variation	[23]
ARSG	OTT7TDW7	Strong	Biomarker	[24]
ARSH	OTG0X9UQ	Strong	Biomarker	[25]
HYAL1	OT2SJN0X	Strong	Biomarker	[26]
HYAL2	OTTVINXW	Strong	Biomarker	[26]
LAMA5	OTIIXE4M	Strong	Biomarker	[27]
MAP1LC3A	OTPMGIU4	Strong	Biomarker	[28]
MPEG1	OT7DAO0F	Strong	Genetic Variation	[20]
PDIA5	OT76ZSX5	Strong	Altered Expression	[29]
RPS27	OTFXKY7P	Strong	Genetic Variation	[20]
SPAM1	OTMPOB4E	Strong	Altered Expression	[30]
TNMD	OTHLVA9G	Strong	Genetic Variation	[28]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7392).
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] ClinicalTrials.gov (NCT03612869) Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA) (AAVance). U.S. National Institutes of Health.
• [7] Clinical pipeline report, company report or official report of Abeona Therapeutics.
• [8] ClinicalTrials.gov (NCT04088734) Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease. U.S. National Institutes of Health.
• [9] ClinicalTrials.gov (NCT04571970) RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome). U.S. National Institutes of Health.
• [10] ClinicalTrials.gov (NCT02702115) Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I. U.S. National Institutes of Health.
• [11] ClinicalTrials.gov (NCT03041324) Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II. U.S. National Institutes of Health.
• [12] ClinicalTrials.gov (NCT03580083) RGX-111 Gene Therapy in Patients With MPS I. U.S. National Institutes of Health.
• [13] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [14] Identification of arylsulfatase B gene mutations and clinical presentations of Iranian patients with Mucopolysaccharidosis VI.Gene. 2019 Jul 20;706:1-5. doi: 10.1016/j.gene.2019.04.050. Epub 2019 Apr 19.
• [15] Mucopolysaccharidosis IVA: submicroscopic deletion of 16q24.3 and a novel R386C mutation of N-acetylgalactosamine-6-sulfate sulfatase gene in a classical Morquio disease.Hum Mutat. 1996;7(2):123-34. doi: 10.1002/(SICI)1098-1004(1996)7:2<123::AID-HUMU6>3.0.CO;2-D.
• [16] Mutation spectrum and pivotal features for differential diagnosis of Mucopolysaccharidosis IVA patients with severe and attenuated phenotype.Gene. 2019 Jul 1;704:59-67. doi: 10.1016/j.gene.2019.04.026. Epub 2019 Apr 11.
• [17] Identification of a novel compound heterozygous IDUA mutation underlies Mucopolysaccharidoses type I in a Chinese pedigree.Mol Genet Genomic Med. 2020 Jan;8(1):e1058. doi: 10.1002/mgg3.1058. Epub 2019 Nov 23.
• [18] Final results of the phase 1/2, open-label clinical study of intravenous recombinant human N-acetyl--d-glucosaminidase (SBC-103) in children with mucopolysaccharidosis IIIB.Mol Genet Metab. 2019 Feb;126(2):131-138. doi: 10.1016/j.ymgme.2018.12.003. Epub 2018 Dec 6.
• [19] An Improved Adeno-Associated Virus Vector for Neurological Correction of the Mouse Model of Mucopolysaccharidosis IIIA.Hum Gene Ther. 2019 Sep;30(9):1052-1066. doi: 10.1089/hum.2018.189. Epub 2019 Jun 4.
• [20] Ophthalmologic manifestations in Taiwanese patients with mucopolysaccharidoses.Mol Genet Genomic Med. 2019 May;7(5):e00617. doi: 10.1002/mgg3.617. Epub 2019 Mar 8.
• [21] Distinct effects of N-acetylgalactosamine-4-sulfatase and galactose-6-sulfatase expression on chondroitin sulfates.J Biol Chem. 2008 Apr 11;283(15):9523-30. doi: 10.1074/jbc.M707967200. Epub 2008 Feb 18.
• [22] Gene silencing of EXTL2 and EXTL3 as a substrate deprivation therapy for heparan sulphate storing mucopolysaccharidoses.Eur J Hum Genet. 2010 Feb;18(2):194-9. doi: 10.1038/ejhg.2009.143. Epub 2009 Aug 19.
• [23] How close are we to therapies for Sanfilippo disease?.Metab Brain Dis. 2018 Feb;33(1):1-10. doi: 10.1007/s11011-017-0111-4. Epub 2017 Sep 18.
• [24] Degeneration of Photoreceptor Cells in Arylsulfatase G-Deficient Mice. Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1120-31. doi: 10.1167/iovs.15-17645.
• [25] Bio-Plex immunoassay measuring the quantity of lysosomal N-acetylgalactosamine-6-sulfatase protein in dried blood spots for the screening of mucopolysaccharidosis IVA in newborn: a pilot study.BMJ Open. 2017 Jul 13;7(7):e014410. doi: 10.1136/bmjopen-2016-014410.
• [26] Conditional knockdown of hyaluronidase 2 in articular cartilage stimulates osteoarthritic progression in a mice model.Sci Rep. 2017 Aug 1;7(1):7028. doi: 10.1038/s41598-017-07376-5.
• [27] Substrate accumulation and extracellular matrix remodelling promote persistent upper airway disease in mucopolysaccharidosis patients on enzyme replacement therapy.PLoS One. 2018 Sep 18;13(9):e0203216. doi: 10.1371/journal.pone.0203216. eCollection 2018.
• [28] Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency.Autophagy. 2018;14(8):1419-1434. doi: 10.1080/15548627.2018.1474313. Epub 2018 Jul 23.
• [29] Unfolded protein response is not activated in the mucopolysaccharidoses but protein disulfide isomerase 5 is deregulated.J Inherit Metab Dis. 2012 May;35(3):479-93. doi: 10.1007/s10545-011-9403-8. Epub 2011 Oct 15.
• [30] Serum hyaluronidase aberrations in metabolic and morphogenetic disorders.Glycoconj J. 2005 Nov;22(7-9):395-400. doi: 10.1007/s10719-005-1390-2.