Canine-Inherited Dystrophinopathies and Centronuclear Myopathies

Abstract

The inherited myopathies include channelopathies, myotonias, metabolic and mitochondrial conditions, congenital myopathies, and muscular dystrophies. This chapter focuses on Duchenne muscular dystrophy (DMD) and one of the centronuclear (congenital) myopathies, X-linked myotubular myopathy (XLMTM). The pattern of disease varies between these two diseases. Initial symptoms principally relate to the appendicular musculature in DMD, with respiratory function becoming impaired in the later stages. In contrast, many XLMTM patients are never able to walk and must receive ventilator support soon after birth. Genetically homologous conditions in dogs, namely, golden retriever muscular dystrophy (GRMD) and XLMTM of Labrador retrievers, are valuable models for preclinical studies. In developing preclinical trials in dogs, the clinical course must be carefully considered. Studies in GRMD dogs are typically conducted over the 3–6-month age period when signs progress relatively quickly. On the other hand, the XLMTM syndrome of Labrador retrievers evolves more rapidly, so affected dogs must be treated and assessed even earlier then 3–6 months. A number of preclinical trials have been conducted in GRMD, in some cases providing support for moving the investigative therapy forward to human trials. While studies in XLMTM dogs have been more limited, promising results have already been seen. Future studies in both of these canine-inherited myopathies should shed further light on homologous human diseases.