Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II

CNS-directed gene therapy for the treatment of neurologic and somatic mucopolysaccharidosis type II (Hunter syndrome)

“…There was no phenotypic description available for this animal model, so we first set out to characterize the effects of Ids deletion on brain and somatic organs of 2-month-old MPSII males. As expected, IDS activity was almost undetectable throughout the encephalon (Supplemental Figure 1A; supplemental material available online with this article; doi:10.1172/jci.insight.86696DS1); the low levels of activity (<0.8%) measured in knockout animals corresponded to background signal of the assay (43). Due to IDS deficiency, all areas of the encephalon presented increased GAG content, which ranged from 121% to 150% of WT values (Supplemental Figure 1B).…”

Hematopoietic Stem Cell Gene Therapy Corrects Neuropathic Phenotype in Murine Model of Mucopolysaccharidosis Type II

“…Total GAGs assays were performed by using Wieslab's sGAG quantitative Alcian blue-binding assay kit (Euro-Diagnostica, Malmö, Sweden), as previously described 21 . The pathological iduronic acid (PIA) assay was performed according to the procedure described by Shimada,et al 22 .…”

“…Preparation of brain sections and immunostaining were performed according to a procedure previously described 21,26 . Sliced sections were incubated with the primary antibodies and visualized by Alexa 555-conjugated anti-rabbit IgG, Alexa 488-conjugated streptavidin (Invitrogen, This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction.…”

“…MPS II mice were analyzed by the Y-maze test, which evaluates short-term memory performance, to investigate the effect of IDS-overexpressed HSCT on behavioral abnormalities (n=3~5, respectively) 21,30,31 . Although spontaneous alternation behavior did not differ between MPS II mice and wild-type mice at 9 weeks old, rates were impaired in a time-dependent manner in MPS II mice (Fig.…”

Determination of the role of injection site on the efficacy of intra-CSF enzyme replacement therapy in MPS IIIA mice

“…Injection of replacement enzyme into ventricular CSF has been carried out in single-injection studies in mouse models of two other lysosomal storage disorders: Krabbe disease [14] and neuronopathic (type II/III) Gaucher disease [39]. Repeat-injection studies have been performed in mice with Niemann-Pick A, Sandhoff disease, neuronopathic Gaucher disease and MPS II [17,[39][40][41], and sustained enzyme delivery (using mini-osmotic pumps) has been explored in late infantile neuronal ceroid lipofuscinosis and metachromatic leukodystrophy mice [15,19]. In all of these investigations, widespread enzyme distribution and a reduction in pathological lesions in the central nervous system were reported, enabling improvements in clinical function.…”