Lamin Protein Flaw
Turns on Heart-Damaging Genes

MDA grantee Howard Worman at Columbia University in New York, a leading physician-scientist in the field of lamin proteins, mutations of which underlie Emery-Dreifuss muscular dystrophy (EDMD) and type 1B limb-girdle MD (LGMD), recently announced that his group has uncovered the molecular connections between at least one lamin gene mutation and heart disease.

The group’s findings were presented at a meeting of the American Society for Cell Biology in San Francisco. It seems that one group of lamins, known as type A lamins, which are produced in almost all cells in the body, may, when flawed, have specific deleterious effects on the heart.

The researchers analyzed cardiac muscle tissue from mice carrying a lamin A gene mutation that causes the chromosome 1 type of human EDMD, a disorder in which heart disease is nearly universal.

Unlike normal mouse hearts, the hearts with the mutated lamin genes showed increased activity of genes for other proteins, called MAP kinases, which have been previously implicated in heart enlargement and heart failure. The investigators say they also found changes in gene activity for three other components that can contribute to cardiac muscle disease.

“The finding that MAP kinases are activated in the heart in this mouse model of Emery-Dreifuss muscular dystrophy,” Worman said, “suggests that inhibitors of these enzymes may be useful as treatments. This, of course, remains to be tested in animal models and, if successful, possibly in human subjects.”