Biomedical Frontiers: Winter 1994, Vol.1, No.2
Giving Cells The Muscle to Diagnose Muscular Dystrophy

Because all the genetic mutations that cause Duchenne's and Becker's muscular dystrophy are not known, clinicians also rely on measuring the muscle-specific protein `dystrophin' to make a diagnosis. If dystrophin is low or absent, dystrophy is confirmed.

A new test, developed by Columbia-Presbyterian Medical Center scientists and collaborators at the University of Turin in Italy and the Fred Hutchinson Cancer Center in Seattle, expands clinicians' ability to detect dystrophin pre- and postnatally. If the assay proves to be reliable, invasive muscle biopsies in fetuses or children may someday become unnecessary (New England Journal of Medicine, Vol. 329, No. 13, Sept. 23, 1993, p. 915).

The assay essentially tricks fibroblasts or prenatal amniocytes and chorionic villus cells to turn into muscle cells and express muscle proteins, such as dystrophin. The research team, led by Dr. Armand Miranda, professor of clinical pathology, took the non-muscle cells and transduced them with a retroviral vector containing the MYOD gene, one member of a gene family causing muscle differentiation. Cells with the new gene fuse and become myotubes, muscle-like tissue in which dystrophin and myosin levels can be measured. Dr. Miranda's research team also has found these myotubes, when innervated in vitro, contract like muscle cells. Results from the NEJM study show transduced fibroblasts from 60 of 61 people with no history of Duchenne's muscular dystrophy produce dystrophin and myosin. Two patients with Becker's muscular dystrophy, a less serious dystrophy, also express dystrophin. But all cultures from nine patients and two fetuses with Duchenne's were dystrophin deficient.

Dr. Miranda is continuing to analyze fetal tissue to determine the test's accuracy for prenatal diagnosis.