Corrective GUSB transfer to the canine mucopolysaccharidosis VII brain.

  title={Corrective GUSB transfer to the canine mucopolysaccharidosis VII brain.},
  author={Aur{\'e}lie Cubizolle and Nicolas Serratrice and Nadia Skander and Marie-Anne Colle and Sandy Ibanes and Aur{\'e}lie Gennetier and Neus Bayo-Puxan and Khalil Mazouni and Franck J.D. Mennechet and B{\'e}atrice Joussemet and Yan Chérel and Yaouen Lajat and Charles H. Vite and Florence Bernex and Vasiliki Kalatzis and Mark E. Haskins and Eric J. Kremer},
  journal={Molecular therapy : the journal of the American Society of Gene Therapy},
  volume={22 4},
Severe deficiency in lysosomal β-glucuronidase (β-glu) enzymatic activity results in mucopolysaccharidosis (MPS) VII, an orphan disease with symptoms often appearing in early childhood. Symptoms are variable, but many patients have multiple organ disorders including neurological defects. At the cellular level, deficiency in β-glu activity leads to abnormal accumulation of glycosaminoglycans (GAGs), and secondary accumulation of GM2 and GM3 gangliosides, which have been linked to… 
Lysosomal and network alterations in human mucopolysaccharidosis type VII iPSC-derived neurons
The interplay between reduced β-gluc activity, GAG accumulation and alterations in neuronal activity is demonstrated, and a human experimental model for elucidating the bases of MPS VII-associated cognitive defects is provided.
CAV-2 Vector Development and Gene Transfer in the Central and Peripheral Nervous Systems
This review focuses on the use of canine adenovirus type 2 (CAV-2) vectors for gene transfer to neurons in the brain, spinal cord, and peripheral nervous system.
Location of the Cell Adhesion Molecule “Coxsackievirus and Adenovirus Receptor” in the Adult Mouse Brain
The coxsackievirus and adenovirus receptor (CAR) is a single-pass transmembrane cell adhesion molecule (CAM). CAR is expressed in numerous mammalian tissues including the brain, heart, lung, and
Canine and Feline Models of Human Genetic Diseases and Their Contributions to Advancing Clinical Therapies

The canine and feline models that are maintained at RCAM are presented here with a focus on preclinical therapy data and clinical studies that have been generated from preclinical work in these models are presented.
Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development
A comprehensive overview of the current state of the field is provided, reviewing the most used viral gene delivery vectors in the context of lysosomal storage disorders, a selection of relevant pre-clinical studies and ongoing clinical trials within recent years.
Adenovirus Tales: From the Cell Surface to the Nuclear Pore Complex
This work accentuates the strikingly diverse mechanisms for AdV entry, comparing human AdV type 5 (HAdV-C5) in epithelial cells and canine type 2 (CAdV2, or commonly referred to as CAV-2) in neurons, and highlights some outstanding questions and hurdles needed to improve vector-mediated gene and vaccine delivery and treatments for Adv disease.
Viral Vector Gene Delivery to the Brain for Treating Neurogenetic Diseases
The three most commonly used viral vectors, herpes simplex viruses (HSVs), lentiviruses and adeno-associated viruses (AAVs) are described, as well as the potential routes of administration for delivery of viral vectors in humans.
Drug and Gene Delivery to the Central Nervous System for Neuroprotection
Recently, due to strong emphasis on environmental awareness worldwide, utilization of renewable feedstocks has been growing in the development of materials for various applications. Amphiphilic
Canine helper-dependent vectors production: implications of Cre activity and co-infection on adenovirus propagation
How Cre and MOI ratio impact adenovirus vectors yields and infectivity is shown, providing key-information to design an improved manufacturing of HDV.


Systemic and Central Nervous System Correction of Lysosomal Storage in Mucopolysaccharidosis Type VII Mice
Results indicate that prolonged enzyme expression from transgenes delivered to deficient liver and brain can mediate pervasive correction and illustrate the potential for gene therapy of MPS and other lysosomal storage diseases.
Intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type VII.
Findings indicate that localized overexpression of GUSB has positive effects on the pathology and cognitive function and does not have overt toxicity, as measured in the Morris Water Maze test.
Long-term and significant correction of brain lesions in adult mucopolysaccharidosis type VII mice using recombinant AAV vectors.
A single intracerebral injection of AAV vectors could achieve a broad and sustained lysosomal enzyme delivery, allowing for stable reversion of storage lesions in a significant fraction of the adult brain.
Production of MPS VII mouse (Gustm(hE540A.mE536A)Sly) doubly tolerant to human and mouse β-glucuronidase
A new MPS VII mouse model is developed, which is tolerant to both human and murine GUS, and should be useful to evaluate therapeutic responses in adult mice receiving repetitive doses of enzyme or mice receiving gene therapy as adults.
Selective neurodegeneration in murine mucopolysaccharidosis VII is progressive and reversible
In the mouse model of mucopolysaccharidosis VII, it is found that specific regions of the brain are vulnerable to neurodegeneration, characterized by the presence of ubiquitin inclusions, neurofilamentInclusions, and reactive astrogliosis.
Safe, efficient, and reproducible gene therapy of the brain in the dog models of Sanfilippo and Hurler syndromes.
In immunosuppressed dogs, vector was efficiently delivered throughout the brain, induced α-N-acetyl-glucosaminidase production, cleared stored compounds and storage lesions, and strongly support projects of human trials aimed at assessing this treatment in Sanfilippo syndrome.
Transgene produces massive overexpression of human β-glucuronidase in mice, lysosomal storage of enzyme, and strain-dependent tumors
  • C. Vogler, N. Galvin, W. Sly
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
These transgenic models show that massive overexpression of a lysosomal enzyme can be associated with dramatic morphological alterations, which, at least in one of the two lines, had little clinical consequence.
Mucopolysaccharidosis IIIB, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response
The data suggest that an autoimmune response directed at CNS components contributes to MPS IIIB neuropathology independent of lysosomal storage pathology.
Overview of the mucopolysaccharidoses.
The clinical features of the MPS disorders and a brief review of treatment options will be presented in order to aid the rheumatologist in recognizing the features of these rare genetic disorders.