Effect of cisternal sulfamidase delivery in MPS IIIA Huntaway dogs—A proof of principle study

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

“…Preclinical studies of intrathecal delivery of a recombinant enzyme (39,(59)(60)(61), now being translated to humans (NCT01155778 and NCT01299727, clinicaltrials.gov), confirm that an increase in sulfamidase levels in CSF can be effective in counteracting the pathological changes associated with MPS IIIA and further support the rationale of our study. While we showed safety and efficacy in MPS IIIA mice and evidence of widespread transgenic expression in dogs using i.c.…”

Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats

“…These results were similar to those found in mature immunotolerized MPS-VI cats (14) and support the contention that repeated IT-INJ is a safe and efficacious means of regularly administering enzyme into the CNS in MPS-VI and other lysosomal storage disorders for which development of paresis needs to be prevented (6,7) or in which brain function is impaired (16,(23)(24)(25)28,29).…”

Innovative Therapeutic Approaches for Improving Patient Life Condition with a Neurological Lysosomal Disease

“…Intrathecal enzyme replacement therapy (ERT) holds promise as a treatment for the central nervous system manifestations of lysosomal storage diseases, since treatment via the cerebrospinal fluid represents a potential method of delivering recombinant enzyme across the blood-brain barrier. All intra-cerebrospinal fluid ERT studies in mice have reported improved function, and reduced neuropathology has also been described in the brain of dog models (MPS I Dickson et al, 2007), MPS IIIA (Hemsley et al, , 2008(Hemsley et al, , 2009). However, several questions remain regarding this approach, in particular which route of injection (ventricular, cisternal or lumbar) provides the most widespread distribution of enzyme in brain parenchyma; is bolus or sustained delivery of enzyme via an osmotic pump device preferable; and, finally, what is the optimal frequency of administration for each condition?…”