Focal lesions following intracerebral gene therapy for mucopolysaccharidosis IIIA

Mucopolysaccharidosis type IIIA (MPSIIIA) caused by recessive SGSH variants results in sulfamidase deficiency, leading to neurocognitive decline and death. No disease‐modifying therapy is available. The AAVance gene therapy trial investigates AAVrh.10 overexpressing human sulfamidase (LYS‐SAF302) delivered by intracerebral injection in children with MPSIIIA. Post‐treatment MRI monitoring revealed lesions around injection sites. Investigations were initiated in one patient to determine the cause.

[1]  J. Muenzer,et al.  Chemically modified recombinant human sulfamidase (SOBI003) in mucopolysaccharidosis IIIA patients: Results from an open, non-controlled, multicenter study. , 2022, Molecular genetics and metabolism.

[2]  J. Muenzer,et al.  A multicenter open-label extension study of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A. , 2021, Molecular genetics and metabolism.

[3]  D. Ballon,et al.  Safety of Direct Intraparenchymal AAVrh.10-mediated CNS Gene Therapy for Metachromatic Leukodystrophy. , 2020, Human gene therapy.

[4]  R. Samulski,et al.  AAV vector mobilization, risk vs reality. , 2020, Human gene therapy.

[5]  A. Pshezhetsky,et al.  Brain Pathology in Mucopolysaccharidoses (MPS) Patients with Neurological Forms , 2020, Journal of clinical medicine.

[6]  A. Pshezhetsky,et al.  Molecular Bases of Neurodegeneration and Cognitive Decline, the Major Burden of Sanfilippo Disease , 2020, Journal of clinical medicine.

[7]  P. Trim,et al.  AAVrh10 Vector Corrects Disease Pathology in MPS IIIA Mice and Achieves Widespread Distribution of SGSH in Large Animal Brains , 2019, Molecular therapy. Methods & clinical development.

[8]  S. van der Sluis,et al.  Vanishing white matter: deregulated integrated stress response as therapy target , 2019, Annals of clinical and translational neurology.

[9]  M. Deijs,et al.  Viral Metagenomics on Cerebrospinal Fluid , 2019, Genes.

[10]  D. Kerr,et al.  Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial. , 2019, Molecular genetics and metabolism.

[11]  B. Bigger,et al.  High dose genistein aglycone in Sanfilippo syndrome: Results of a randomized, double-blinded, placebo controlled clinical trial , 2019, Molecular Genetics and Metabolism.

[12]  V. Yong,et al.  The extracellular matrix: Focus on oligodendrocyte biology and targeting CSPGs for remyelination therapies , 2018, Glia.

[13]  M. S. van der Knaap,et al.  Vanishing white matter: a leukodystrophy due to astrocytic dysfunction , 2018, Brain pathology.

[14]  C. Proud,et al.  Proteomic and Metabolomic Analyses of Vanishing White Matter Mouse Astrocytes Reveal Deregulation of ER Functions , 2017, Frontiers in Cellular Neuroscience.

[15]  T. Gloster,et al.  The Enzymatic Degradation of Heparan Sulfate. , 2017, Protein and peptide letters.

[16]  R. Herzog.  Complexity of immune responses to AAV transgene products - Example of factor IX. , 2017, Cellular immunology.

[17]  S. Back.  White matter injury in the preterm infant: pathology and mechanisms , 2017, Acta Neuropathologica.

[18]  P. Haslett,et al.  A Prospective Natural History Study of Mucopolysaccharidosis Type IIIA. , 2016, The Journal of pediatrics.

[19]  Yow-Ming C Wang,et al.  Immune response to enzyme replacement therapies in lysosomal storage diseases and the role of immune tolerance induction. , 2016, Molecular Genetics and Metabolism.

[20]  J. Fawcett,et al.  “GAG-ing with the neuron”: The role of glycosaminoglycan patterning in the central nervous system , 2015, Experimental Neurology.

[21]  Etiena Basner-Tschakarjan,et al.  AAV capsid CD8+ T-cell epitopes are highly conserved across AAV serotypes , 2015, Molecular therapy. Methods & clinical development.

[22]  A. Ballabio,et al.  Intracerebral administration of adeno-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with mucopolysaccharidosis type IIIA disease: results of a phase I/II trial. , 2014 .

[23]  Q. Waisfisz,et al.  Exome sequencing reveals mutated SLC19A3 in patients withan early-infantile, lethal, encephalopathy , 2013, Brain : a journal of neurology.

[24]  S. Olabarriaga,et al.  Performance of VIDISCA-454 in Feces-Suspensions and Serum , 2012, Viruses.

[25]  A. Ballabio,et al.  Autophagy in lysosomal storage disorders , 2012, Autophagy.

[26]  G. Węgrzyn,et al.  Genistein in Sanfilippo disease: A randomized controlled crossover trial , 2012, Annals of neurology.

[27]  Steven P. Miller,et al.  Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants , 2012, Annals of neurology.

[28]  M. Habek,et al.  Pathology of acute disseminated encephalomyelitis , 2011 .

[29]  H. Prange,et al.  „Vanishing white matter disease“ , 2011, Der Nervenarzt.

[30]  D. Zafeiriou,et al.  Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece , 2011, American journal of medical genetics. Part A.

[31]  S. Goldman,et al.  Defective Glial Maturation in Vanishing White Matter Disease , 2011, Journal of neuropathology and experimental neurology.

[32]  G. Scheper,et al.  Leukoencephalopathy With Vanishing White Matter: A Review , 2010, Journal of neuropathology and experimental neurology.

[33]  B. Poorthuis,et al.  Sanfilippo syndrome: A mini-review , 2008, Journal of Inherited Metabolic Disease.

[34]  R. Mandel,et al.  Immune responses to adenovirus and adeno-associated vectors used for gene therapy of brain diseases: the role of immunological synapses in understanding the cell biology of neuroimmune interactions. , 2007, Current gene therapy.

[35]  D. Spillmann,et al.  Characterization of Anti-heparan Sulfate Phage Display Antibodies AO4B08 and HS4E4* , 2007, Journal of Biological Chemistry.

[36]  Atul Mehta,et al.  Lysosomal Storage Disorders , 2005 .

[37]  Mahendra S Rao,et al.  Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation , 2005, Nature Medicine.

[38]  A. Hoogeveen,et al.  A fluorimetric enzyme assay for the diagnosis of sanfilippo disease type A (MPS IIIA) , 1996, Journal of Inherited Metabolic Disease.

[39]  J. Hopwood,et al.  Diagnosis of Sanfilippo type A syndrome by estimation of sulfamidase activity using a radiolabelled tetrasaccharide substrate. , 1982, Clinica chimica acta; international journal of clinical chemistry.

[40]  A. T. van der Ploeg,et al.  Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III. , 2015, JIMD reports.

[41]  P. Scheffer,et al.  Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease. , 2013, Brain : a journal of neurology.

[42]  K. Kimata,et al.  Sulfation pattern in glycosaminoglycan: Does it have a code? , 2004, Glycoconjugate Journal.

[43]  V. Cool,et al.  Poor cognitive outcome of eleven children with Sanfilippo syndrome after bone marrow transplantation and successful engraftment , 1995 .