Table 5 Summary of MPS clinical research

MPS I

α-l-iduronidase

Recombinant human IDUA, followed by Pentosan polysulphate (PPS)

ERT: IV

PPS: SQ

↓ uGAGs*; Improved joint mobility and range of motion; Decreased pain

4

Hennermann et al., 2016 [186]

Recombinant human IDUA, IgG fusion

IV

Stabilized developmental quotient, GM volume, & uGAGs; Improvement in joint mobility*;

Reduced spleen and liver volume*

11

Giugliani et al., 2018 [111]

IgG Fusion (HIR)

IV

Increased plasma clearance in children compared to adults*

5 adults

13 children

Pardridge et al., 2018 [35]

MPS II

Iduronidase-2-sulfate

Recombinant human I2S

IV

↓ uGAGs*; Improvements in endurance (6MWT)*

31

Sohn et al., 2013 [113]

IDDD

 > 70% ↓ CSF GAGs

12

Muenzer et al., 2016 [112]

Recombinant human I2S with anti-human transferrin receptor antibody (JR-141)

IV

↓ CSF GAGs*; ↓ plasma and uGAGs

14

Okuyama et al., 2019 [115]

↓ CSF GAGs*;↓ serum GAGs; Stabilized endurance

28

Okuyama et al., 2021 [36]

↓ CSF GAGs* (2.0-mg/kg); Decreased liver and spleen volume; Improvement of neurocognition; Stabilized cortical GM volume

20

Giugliani et al., 2021 [116]

MPS IIIA

Heparan-N-sulfatase

Recombinant human HNS

IDDD

↓ CSF heparan sulfate; ↓ uGAGs

12

Jones et al., 2016 [117]

IT

↓ CSF GAGs; ↓ uGAGs*

14

Wijburg et al., 2019 [118]

MPS IIIB

α-N-acetylglucosamine

6-sulfatase

Recombinant human NAGLU, AAV encoded

(rAAV2/5)

IP

Enzyme activity found; Improved neurocognition

7

Tardieu et al., 2017 [187]

MPS IVA

N-acetylgalactoasmine-6-sulfate sulfatase

Recombinant Human GALNS

IV

↓ urinary Keratin Sulfate; Improved endurance (6MWT, 3MSC) and respiratory function

117

Hendriksz et al., 2015 [121]

Improvements in exercise capacity, muscle strength, and pain

25

Burton et al., 2015 [120]

Stabilized endurance, respiratory function, and ability to perform ADLs‡

20

Hendriksz et al., 2018 [37]

MPS VI

N-acetylgalactosamine 4-sulfatase

Recombinant human ARSB

IV

↓ uGAGs*; Improved 12MWT compared to placebo*

19

Harmatz et al., 2005 [38]

MPS VII

β-Glucuronidase

Recombinant human GUSB

IV

↓ uGAGs*; ≥ 1 improvement in Multi-Domain Responder Index category in 10/12 patients

12

Harmatz et al., 2018 [39]

↓ uGAGs*

23

Qi et al., 2018 [123]

↓ uGAGs

3

Cadaoas et al., 2020 [20]

↓ uGAGs*; Reduction of fatigue; Stabilized visual acuity, joint mobility, fine motor skills

12

Wang et al., 2020 [122]

↓ uGAGs*

3

Jones et al., 2021 [188]