Micro-utrophin Therapy for Duchenne Muscular Dystroph

Duan D. Micro-utrophin Therapy for Duchenne Muscular Dystrophy. Molecular therapy : the journal of the American Society of Gene Therapy 2019


Duchenne muscular dystrophy (DMD) is a
deadly muscle disease caused by the loss of
dystrophin, a critical subsarcolemmal protein
that maintains muscle integrity during
contraction. Dystrophin protects muscle
cells by linking the cytoskeleton and the
extracellular matrix. Interestingly, this function
can also be accomplished by another
cellular protein called utrophin. Transgenic
overexpression of utrophin or mini-utrophin
markedly prevented muscle disease in dystrophin-
deficient mdx mice. Since utrophin
is not a foreign protein to DMD patients
(thus minimizing the risk of immune responses)
and can functionally substitute for
dystrophin, there has been a substantial interest
in developing utrophin-based gene
therapy. The therapeutic potential of the
massively miniaturized utrophin gene (Figure
1) was demonstrated by the Chamberlain
lab in the phenotypic dystrophin/utrophin
double knockout mouse via intravenous injection
of the adeno-associated virus (AAV)
micro-utrophin vector.1 To translate AAV
micro-utrophin therapy to DMD patients,
an immediate next step is to scale up and
validate the finding in the symptomatic
canine model. A recent study by Song
et al.,2 published in Nature Medicine,
addresses this important question.

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