Transcript therapeutic approaches and perspective

THERAPEUTIC APPROACHES
AND PERSPECTIVE

Over the last few years a range of approaches
have been developed that aim to correct the
genetic defect, restore functional expression of
dystrophin, slow disease progression, and improve
the life quality of DMD patients.

These can roughly be categorized into three
classes —
genetic, cell-based, and pharmacological
approaches (药理方法)
Genetic

Gene transfer
A functional dystrophin gene could be inserted into
dystrophy muscle cells to compensate for the defective
gene copy. Recombinant adeno- associated viruses (AAV)
possess some advantages of conventional adnoviral and
retroviral vectors and lentiviral vectors, and are
increasingly being used to carry the mini-, micro-dystrophin,
or utrophin genes into the skeletal and heart cells of mdx
mice.

Gene modification
The aim of gene modification is to change or repair
gene mutations. Among the most promising approaches is
exon skipping, which attempts to turn a Duchenne mutation
into a less severe Becker form .
There is a gene therapy method known as targeting
repairing or chimeraplast, using a synthetic blend of DNA
and the related RNA, which tricks the patient's own cells to
repair the mutation. The chimeraplasts match the patients'
own DNA except for where the mutation occurs, attach to
the DNA, and then activate DNA repair mechanisms.
cell-based

Cell therapy（细胞治疗）
Muscular satellite cells, which positioned between the
plasma membrane and the surrounding basal membrane
of mature muscle fibers, are considered to represent
muscular stem cells. Satillite cells alone are sufficient to
mediate extensive regeneration of damaged adult skeletal
muscle in vivo.
The efficacy of bone marrow cells, or even single
hematopoietic（造血的） stem cells, in the repair of
muscle injury has been extensively explored. MSCs can
participate in myogenesis both in vitro and in vivo,
regenerating myofibers and sublminar Pax-7+ satellite cells
in mdx/nude mice.

Utrophin
Utrophin is a protein with similar structure to
dystrophin and can be found in high concentrations within
muscle cells during fetal development. After birth the
expression shifts to the neuromuscular junction.
Substantially increasing levels of utrophin protein by
introducing a utrophin gene driven by a constitutive or a
muscle -pecific promoter (or using chemicals that
upregulate the promoter acitvity of the endogenous
utrophin gene) could prevent the pathology of muscular
dystrophy.
Pharmacological approaches

A broad range of pharmacological strategies for
DMD are being exploited. These include steroid
treatment, maintaining calcium homeostasis,
decreasing inflammation, increasing muscle
strength, suppressing stop codons, upregulation of
utrophin, and increasing muscle mass via
modulation of growth/developmental factors.
PERSPECTIVE

Advances in understanding diseases in recent
years have opened the door for therapeutic
interventions. Research aiming to further reveal
the properties of dystrophic muscle fibres and in
stem cell biology will harness the clinical use of
different therapeutic approaches. It is most likely
that only a combination of multiple approaches will
eventually lead to the development of treatments.