The pathogenesis of Duchenne muscular dystrophy: significance of experimental observations

Abstract

The pathogenesis of Duchenne muscular dystrophy (DMD) remains elusive, but as this is an inherited condition the primary manifestation of the disease is assumed to be in the regulatory control or biosynthesis of a protein. Current hypotheses attribute the pathological state of skeletal muscle in DMD to a defect in the nerve supply, or in the vasculature, or in the muscle itself. However, various tissues other than skeletal muscle are also affected; thus the current view of DMD requires reevaluation. The following possibilities should be considered: That the primary lesion is expressed in one of the major communication systems (nervous, vascular, or endocrine). That the primary lesion is expressed in a specific tissue: a) if in skeletal muscle, alterations in non-muscular tissues must be due to the release of muscle constituents into extracellular fluid; b) if in a non-muscular tissue, this might produce too much (or too little or none) of a constituent normally secreted into the extracellular fluid, or produce a "toxic" agent. That the primary lesion is expressed in a wide variety of tissues: the effect on a particular tissue will depend entirely upon the degree of requirement of the altered protein for function.