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.
Corrective GUSB transfer to the canine mucopolysaccharidosis VII cornea using a helper-dependent canine adenovirus vector.
CAV-2-Mediated GFP and LRRK2G2019S Expression in the Macaca fascicularis Brain
The studies demonstrate the neuronal tropism, retrograde transport, biodistribution, and efficacy of CAV-2 vectors expressing GFP and leucine-rich repeat kinase 2 (LRRK2G2019S) in the Macaca fascicularis brain and suggest that following optimization CAV -2-mediated LRRK-2G 2019S expression could help model the neurodegenerative processes of this genetic subtype of Parkinson’s disease in monkeys.
Large animal models contribute to the development of therapies for central and peripheral nervous system dysfunction in patients with lysosomal storage diseases.
This review article will summarize the large animal models available for study as well as their contributions to the development of central and peripheral nervous system dysfunction in LSDs.
Coxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity
The role of the coxsackievirus and adenovirus receptor (CAR), a single-pass cell adhesion molecule, in the adult brain is addressed and it is demonstrated that CAR is expressed by mature neurons throughout the brain.
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.
CAV-2--why a canine virus is a neurobiologist's best friend.


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.