Myogenic defect in human muscular dystrophy

Abstract

THE aetiology of muscular dystrophy has been considered to be either myagenic or neurogenic¹. Much of the evidence has been obtained from studies of muscle in tissue culture using animal² or human³ sources. Although results have often been equivocal^4,5 the most recent studies have failed to show any morphological differences between normal and abnormal muscle^3,6,7. Hence, it could be argued that the primary defect is not in the muscle but rather may be in the nerve which innervates the muscle⁶. But, almost all of these studies have involved techniques based on explants of small muscle pieces, which muscle fragments then typically require one week for outgrowth from the tissue pieces and a further week or two before differentiated function (myotube formation) is seen^3,6. For expression of maximally differentiated cultures (cross striations and spontaneous contractions) it has been presumed that innervation may be required, since contractions are rarely found and are essentially seen only in the presence of added nerve cells⁶. We have recently described a new technique for establishing fully differentiated adult muscle cultures from mononucleated cells and have found spontaneous contractions without the requirement for nerve cells⁸. Using this method, we have compared the maturation of muscle from the Duchenne (X-linked recessive) form of muscular dystrophy with appropriate control cases, and have found an abnormality in cellular behaviour restricted to the Duchenne material.