Muscling in

-- THE ideal way of curing an inherited disorder would be to adopt gene therapy
(correct the genetic defect). Failing that,
it would be worth exploring whether the
severity of the disorder might be ameliorated by substituting a functional
gene product - protein - in place of the dysfunctional product (or no
product).

One of the most novel concepts to
have emerged in recent years in the area
of gene therapy is the possible use of
muscles as factories for the production
and release of proteins. The basic idea is
simple. A gene encoding the therapeutic
protein of interest is incorporated into a
virus, or into what is known as a
vector'. The virus is then used to
infect primary myoblasts - multi-
nucleate muscle cells capable of
prolonged division - that are isolated
from the skeletal muscle tissue of
the host.

These myoblasts are capable of
synthesising the desired protein and
are now implanted into the tissue of
the patient. It is possible that the
patient's own cells may not be capable
ofserving the purpose, in which case the
myoblasts will need to be borrowed
from a healthy donor with a host-compatible immune system.

Much of the pioneering research in
this area has been done by Jyotsna
Dhawan, Helen Blau and colleagues at
the Stanford University School of
Medicine, us. The work had till recently
been concentrated on mice. The only
clinical application of myoblast transplantation so far has involved an
attempt to treat Duchenne muscular
dystrophy, a progressive disorder of
muscles; the results have been disappointing. It is envisaged, however, that
more systematic human trials might
begin in the near future.

The uses of myoblast transplantation, include transfer to the circulation
of (normally) non-muscle proteins such
as growth hormones and blood coagulation factors, delivery of protein vaccines
by transforming the donor muscle cells
with the DNA that encodes the desired
vaccine and nerve regeneration induced
by the release of nerve growth factors by
the injected myoblasts. Of all the uses of
this therapy that have been talked about,
the one that strikes the imagination
most concerns the heart, where its practice could promote fresh vascularisation
so as to improve blood flow and repair
cardiac tissue damaged by a heart
attack.