SMALL PROTEIN-MEDIATED THERAPY FOR THE TREATMENT OF MUSCULAR DYSTROPHY
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UCLA Technology Available For Licensing |
BACKGROUND: There are more than 20 categories of muscular
dystrophy, all of which are caused by genetic defects that cause progressive muscle
weakness, altered muscle proteins, and muscle cell and tissue death. Duchenne
muscular dystrophy (DMD) is the most common muscular dystrophy, in which the loss
of function in the dystrophin gene compromises the dystrophin-glycoprotein complex
(DGC) in the sarcolemma. In the absence of DGC, the sarcolemma loses its mechanical
stability during muscle contraction. Current therapeutic strategies for DMD are
focused on introducing different recombinant dystrophin genes into dystrophic
muscles using viral-mediated vectors. However, one of its limitations is the size
of the dystrophin cDNA, which is too large to package into currently available
viral vectors. Although microdystrophin can be packaged into viral vectors, expression
of non-native, recombinant dystrophin can potentially elicit an immune response
that may cause severe muscle degeneration. New therapeutic approaches are therefore
needed for the treatment of muscular dystrophy.
INNOVATION: UCLA investigators have identified a small
protein that can mitigate muscular dystrophy as demonstrated in dystrophin-deficient
mdx mice. Transverse cryosections of whole quadriceps muscle from age-matched
mdx mice showed near normal muscle structure in the mice with overexpression
of the protein. This protein acts by restoring a functional linkage between
the extracellular matrix and the intracellular actin cytoskeleton. The cDNA
for this protein is under 1-kb—well within the range for efficient packaging
into currently available vectors. The protein is also present in a variety of
non-muscle tissues; hence its increased expression in skeletal muscle is unlikely
to pose an immune threat. The data reveal a hitherto unknown role of this small
protein in the generation and maintenance of functional DGC complex, and opens
up a new therapeutic avenue for the treatment of muscular dystrophy.
POTENTIAL APPLICATIONS
Therapeutics for the treatment of DMD through:
- Viral vector-based gene delivery
- Small molecule-mediated upregulation of protein expression
ADVANTAGES
- Small cDNA that can be packaged efficiently into viral vectors
- Reduced risks of triggering an immune response
DEVELOPMENT-TO-DATE: Investigators have shown that the
protein restores muscle function in mdx mice, an established model for
DMD.
Reference: UCLA Case No. 2007-145
For additional technical details and current licensing
availability,
please contact the following UCLA office:
UCLA Office of Intellectual Property
11000 Kinross Avenue, Suite #200
Los Angeles, CA 90095-7231
Tel: 310-794-0558 Fax: 310-794-0638
email: ncd@research.ucla.edu
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NCD URL: http://www.research.ucla.edu/tech/ucla07-145.htm
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UCLA Technologies Available for
Licensing
http://www.research.ucla.edu/oipa/industry
Copyright © 2007 The Regents of the
University of California.
keywords: muscular dystrophy, duchenne, therapeutic, dystrophin, viral vector, muscle, dystrophin glycoprotein, sarcolemma
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