Functional correction of CNS lesions in an MPS-IIIA mouse model by intracerebral AAV-mediated delivery of sulfamidase and SUMF1 genes

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

“…Adenoassociated virus (AAV) vector-mediated gene transfer, in particular, has shown promising results as an in vivo gene transfer tool, showing longterm production of therapeutic proteins in animal models and in humans (14)(15)(16). Extensive gene delivery to the CNS using AAV vectors has been achieved by multiple direct injections into the brain parenchyma (17,18) or by delivery to the cerebrospinal fluid (CSF) (19)(20)(21). Direct delivery of AAV vectors to the brain parenchyma is being clinically explored in MPS IIIA.…”

Current and emerging treatments and surgical interventions for Morquio A syndrome: A review

“…In-vivo studies have shown that the co-expression of other sulfatases with SUMF1 induces a significant elevation of GALNS enzyme activity. 74,75 However, the optimal ratio between the individual sulfatase and SUMF1 has not been fully investigated. The GALNS gene was transduced with or without SUMF1 into HEK293 cells, human MPS IVA fibroblasts, and mouse MPS IVA chondrocytes using AAV2 vectors.…”

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

“…More recently, a widespread enzymatic correction of CNS tissues was obtained after one single intracerebral injection of therapeutic lentiviral vector in leukodystrophy mouse models (Lattanzi et al, 2010). Several other teams have shown promising results in MPS IIIB, MPS I, MPS IIIA mouse or dog models, using either intracranial AAV-mediated gene therapy (Heldermon et al, 2010;Ellinwood et al, 2011;McIntyre et al, 2010;Fraldi et al, 2007) or intracisternal AAV gene transfer (Fu et al, 2010).…”

“…Inflammation is known to be implicated in numerous neurodegenerative diseases, and has been recently well characterized in murine models of GM1/GM2 gangliosidoses (Myerowitz et al, 2002, Jeyakumar et al, 2003, as well as in mouse models of Metachromatic Leukodystrophy (Hess et al, 1996), Niemann-Pick C disease (German et al, 2002), MPS I (Ohmi et al, 2003), MPS IIIB (Ohmi et al, 2003;Villani et al, 2007) and MPS IIIA (Fraldi et al, 2007). Moreover, our previous study on a mouse model of MPS VII showed an extensive upregulation of genes related to an inflammatory process dominated by activated microglia, astrogliosis and celldeath, suggesting that inflammation might participate in neurodegeneration (Richard et al, 2008).…”