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 theseverity of the disorder might be ameliorated by substituting a functionalgene product - protein - in place of the dysfunctional product (or noproduct).

One of the most novel concepts tohave emerged in recent years in the areaof gene therapy is the possible use ofmuscles as factories for the productionand release of proteins. The basic idea issimple. A gene encoding the therapeuticprotein of interest is incorporated into avirus, or into what is known as avector'. The virus is then used toinfect primary myoblasts - multi-nucleate muscle cells capable ofprolonged division - that are isolatedfrom the skeletal muscle tissue ofthe host.

These myoblasts are capable ofsynthesising the desired protein andare now implanted into the tissue ofthe patient. It is possible that thepatient's own cells may not be capableofserving the purpose, in which case themyoblasts will need to be borrowedfrom a healthy donor with a host-compatible immune system.

Much of the pioneering research inthis area has been done by JyotsnaDhawan, Helen Blau and colleagues atthe Stanford University School ofMedicine, us. The work had till recentlybeen concentrated on mice. The onlyclinical application of myoblast transplantation so far has involved anattempt to treat Duchenne musculardystrophy, a progressive disorder ofmuscles; the results have been disappointing. It is envisaged, however, thatmore systematic human trials mightbegin in the near future.

The uses of myoblast transplantation, include transfer to the circulationof (normally) non-muscle proteins suchas growth hormones and blood coagulation factors, delivery of protein vaccinesby transforming the donor muscle cellswith the DNA that encodes the desiredvaccine and nerve regeneration inducedby the release of nerve growth factors bythe injected myoblasts. Of all the uses ofthis therapy that have been talked about,the one that strikes the imaginationmost concerns the heart, where its practice could promote fresh vascularisationso as to improve blood flow and repaircardiac tissue damaged by a heartattack.