Table 1.

Comparison of advantage and disadvantage of ERT, HSCT and new candidate therapies for MPS IVA.

	Advantage	Disadvantage
ERT	Low risk of mortality and morbidity	High cost ($ 400,000 per year per 25 kg)
	No limitation of age	Weekly infusion
	No specialized medical facility required	Short half-life time of the enzyme (40 min-human, 2 min-mouse)
HSCT	Lower cost than ERT (approximately $ 100,000)	Risk of mortality and morbidity
	One-time permanent treatment	Limitation of age
	Continuous activity of enzyme	Specialized medical facility required
	More effect in bone pathology than ERT	GVHD
		Availability of a donor
	Advantage	Problems to overcome
SDET	Enzyme is active in neutral pH (May work in circulation and ECM)	Immunogenicity to the enzyme
	No age limitation	Optimal dose and treatment frequency
Gene therapy	One-time permanent treatment	Vector selection needs to be determined
	Continuous activity of enzyme	(optimal promoter, AAV serotype, dose etc)
	Does not require donor	Readministration is Not available
	No age limitation	Unknown duration of enzyme expression
Nanomedicine	Protection of enzyme degradation	Limitation on components to make nanoparticles
	Greater permeability through biological membranes	Optimal dose and treatment frequency
	Better efficacy to act on lysosomes	Unknown effects still in animal model
	No age limitation
Pharmacological chaperone therapy	Wide distribution in tissues	Off-target effect
	Oral administration	Optimal dose and treatment frequency
	No immunogenecity	Unknown effects still in animal model

Abbreviation: ERT: enzyme replacement therapy, HSCT: hematopoietic stem cell transplantation, GVHD: graft versus host disease, SDET: substrate degradation enzyme thera.