There occurs a progressive weakness and wastage of skeletal muscle in different
types of muscular dystrophy. The loss of muscle fibers in dystrophic muscle with
impaired function is associated with leakage of intracellular enzymes,
maldistribution of electrolyte content and metabolic defects in myocytes. Marked
increases in the sarcolemma (SL) Na-K ATPase and
Ca/Mg-ecto ATPase activities, as well as depressions in the
sarcoplasmic reticulum (SR) Ca-uptake and Ca-pump ATPase activities
were seen in dystrophic muscles of a hamster model of myopathy. In addition,
impaired mitochondrial oxidative phosphorylation and decrease in the high energy
stores as a consequence of mitochondrial Ca-overload were observed in
these myopathic hamsters. In some forms of muscular dystrophy, it has been shown
that deficiency of dystrophin produces marked alterations in the SL permeability
and promotes the occurrence of intracellular Ca-overload for inducing
metabolic defects, activation of proteases and contractile abnormalities in
dystrophic muscle. Increases in SR Ca-release channels, SL
Na-Ca exchanger and SL store-operated Ca-channels have been
reported to induce Ca-handling abnormalities in a mouse model of muscular
dystrophy. Furthermore, alterations in lipid metabolism and development of
oxidative stress have been suggested as mechanisms for subcellular remodeling and
cellular damage in dystrophic muscle. Although, several therapeutic interventions
including gene therapy are available, these treatments neither fully prevent the
course of development of muscular disorder nor fully improve the function of
dystrophic muscle. Thus, extensive reasearch work with some novel inhibitors of
oxidative stress, SL Ca-entry systems such as store-operated
Ca-channels, Na-Ca exchanger and Ca/Mg-ecto
ATPase (Ca-gating mechanism), as well as SR Ca-release and
Ca-pump systems needs to be carried out in combination of gene therapy for
improved beneficial effects in muscular dystrophy.