. Author manuscript; available in PMC: 2016 Jan 31.

Published in final edited form as: Mol Genet Metab. 2014 Oct 7;114(2):83–93. doi: 10.1016/j.ymgme.2014.09.011

Table III.

Enzymatic and metabolic effects of sustained SGSH activity in MPS IIIA mice

Target	Vector/Dos^a	Age treated/tested	SGSH activity at termination (%WT)			Brain pathology
Target	Vector/Dos^a	Age treated/tested	Liver	Serum	Brain	GAG or Storage vacuoles	Neuroinflammation
AAV APPROACH
Unmodified mSGSH [79, 84, 96]
Liver	AAV8 (LSP1) @10¹²VG/mouse	8wk/10mo	F: 100%	150%	~4%	F: No reduction	n/a^b
	AAV8 (LSP1) @10¹²VG/mouse	8wk/10mo	M: 400%	450%	10%	M: 50% reduced

Blood	AAV9(CAG) @7×10¹²VG/mouse	2mo/10mo	F: 100%	F: 100%	6-8%	GAG corrected SV reduced	near-resolved
	AAV9(CAG) @7×10¹²VG/mouse	2mo/10mo	M: 500%	M: 500%	7-13%	GAG corrected SV reduced	near-resolved

CSF	AAV9 (CAG) @5×10¹⁰VG/mouse	2mo/4mo	F: 20% M: 190%	20% 190%	7-39% 11-36%	corrected corrected except caudal part	resolved resolved
	AAV9 (CAG) @5×10⁹VG/mouse					no reduction	n/a
Fusion IDSsp-hSGSH-ApoB [119]
Liver	AAV2/8 (LSP2) @10¹¹VG/mouse	1mo/7mo	%WT n/a 700%^c	%WT n/a 200%^c	%WT n/a^b 13%^c	near-corrected	resolved
LV- HSC APPROACH
“Unmodified” cohSGSH [120]
Blood	LV- (CD11b) @1.2-1.3VG/cell	2wk/8mo	60%	n/a^b	11%	HS corrected	resolved in cortex and amygdala reduced in most regions

VG, vector genomes; the murine (m) or human (h) SGSH expression cassettes have either of the following promoters: liver-specific LSP1= ApoEHCRhAAT; LSP2= thyroxine-binding globulin promoter; myeloid-specific = CD11b; co-codon-optimized hSGSH

n/a, data not available

relative to heterozygote values