Saying NO to muscular dystrophy

According to the prevailing model for Duchenne muscular dystrophy (DMD) pathogenesis, a lack of dystrophin protein makes muscle cells susceptible to mechanical damage, leading to muscle breakdown. On page 123, Wehling et al. suggest that the major damage in DMD may actually be caused by a secondary consequence of dystrophin loss: destruction of muscle tissue by a patient's own macrophages.

Dystrophin forms a complex with several other proteins, including nitric oxide synthase (NOS). In dystrophin-deficient muscles, such as those of the mdx mouse, a model for DMD, NOS expression is decreased. Reasoning that the loss of nitric oxide's anti-inflammatory activity might exacerbate muscle breakdown, the authors introduced a transgene to produce normal levels of NOS in the muscles of mdx mice. The transgene reduced the concentrations of macrophages in the muscles and prevented...