507. AAV-Mini-Agrin for Laminin-alpha2 Deficient CMD

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Partial laminin alpha2 chain restoration in alpha2 chain-deficient dy/dy mouse by primary muscle cell culture transplantation

Laminin-2 is a component of skeletal and cardiac basal lamina expressed in normal mouse and human. Laminin alpha2 chain (LAMA2), however, is absent from muscles of some congenital muscular dystrophy patients and the dystrophia muscularis (dy/dy) mouse model. LAMA2 restoration was investigated following cell transplantation in vivo in dy/dy mouse. Allogeneic primary muscle cell cultures expressi...

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Amelioration of laminin-alpha2-deficient congenital muscular dystrophy by somatic gene transfer of miniagrin.

Congenital muscular dystrophy (CMD) is characterized by severe muscle wasting, premature death in early childhood, and lack of effective treatment. Most of the CMD cases are caused by genetic mutations of laminin-alpha2, which is essential for the structural integrity of muscle extracellular matrix. Here, we report that somatic gene delivery of a structurally unrelated protein, a miniature vers...

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Deficiency of alpha2-laminin (merosin) underlies classical congenital muscular dystrophy in humans and dy/dy muscular dystrophy in mice and causes severe muscle dysfunction in both species. To gain greater insight into the biochemical and molecular events that link alpha2-laminin deficiency with muscle fiber necrosis, and the associated compensatory responses, gene expression profiles were char...

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Agrin Binds to the Nerve–Muscle Basal Lamina via Laminin

Agrin is a heparan sulfate proteoglycan that is required for the formation and maintenance of neuromuscular junctions. During development, agrin is secreted from motor neurons to trigger the local aggregation of acetylcholine receptors (AChRs) and other proteins in the muscle fiber, which together compose the postsynaptic apparatus. After release from the motor neuron, agrin binds to the develo...

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Linker molecules between laminins and dystroglycan ameliorate laminin-α2–deficient muscular dystrophy at all disease stages

Mutations in laminin-alpha2 cause a severe congenital muscular dystrophy, called MDC1A. The two main receptors that interact with laminin-alpha2 are dystroglycan and alpha7beta1 integrin. We have previously shown in mouse models for MDC1A that muscle-specific overexpression of a miniaturized form of agrin (mini-agrin), which binds to dystroglycan but not to alpha7beta1 integrin, substantially a...

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ژورنال

عنوان ژورنال: Molecular Therapy

سال: 2015

ISSN: 1525-0016

DOI: 10.1016/s1525-0016(16)34116-8