[show abstract][hide abstract] ABSTRACT: Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy in humans and syndromes in mice, dogs, and cats. Affected humans and dogs have progressive disease that leads primarily to muscle atrophy. Mdx mice progress through an initial phase of muscle hypertrophy followed by atrophy. Cats have persistent muscle hypertrophy. Hypertrophy in humans has been attributed to deposition of fat and connective tissue (pseudohypertrophy). Increased muscle mass (true hypertrophy) has been documented in animal models. Muscle hypertrophy can exaggerate postural instability and joint contractures. Deleterious consequences of muscle hypertrophy should be considered when developing treatments for muscular dystrophy.
Physical Medicine and Rehabilitation Clinics of North America 02/2012; 23(1):149-72, xii. · 1.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene- and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. Various phenotypic tests have been developed to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these tests are routinely used in clinical veterinary practice, while others require specialized equipment and expertise. By comparing serial measurements from treated and untreated groups, one can document improvement or delayed progression of disease. Potential treatments for DMD may be broadly categorized as molecular, cellular, or pharmacologic. The GRMD model has increasingly been used to assess efficacy of a range of these therapies. A number of these studies have provided largely general proof-of-concept for the treatment under study. Others have demonstrated efficacy using the biomarkers discussed. Importantly, just as symptoms in DMD vary among patients, GRMD dogs display remarkable phenotypic variation. Though confounding statistical analysis in preclinical trials, this variation offers insight regarding the role that modifier genes play in disease pathogenesis. By correlating functional and mRNA profiling results, gene targets for therapy development can be identified.
[show abstract][hide abstract] ABSTRACT: 2 full-sibling male German Shorthaired Pointer (GSHP) puppies (dogs 1 and 2) with X-linked muscular dystrophy and deletion of the dystrophin gene (gene symbol, DMD) each had poor growth, skeletal muscle atrophy, pelvic limb weakness, episodic collapse, and episodes of coughing.
Initial examination revealed stunted growth, brachygnathism, trismus, and diffuse neuromuscular signs in each puppy; clinical signs were more severe in dog 2 than in dog 1. Immunohistochemical analysis revealed a lack of dystrophin protein in both dogs. During the next 3 years, each dog developed hyperinflation of the lungs, hypertrophy of the cervical musculature, and hypertrophy of the lateral head of the triceps brachii muscle.
Monitoring and supportive care were provided at follow-up visits during an approximately 7-year period. No other specific treatment was provided. Neuromuscular signs in both dogs remained stable after 3 years of age, with dog 2 consistently more severely affected than dog 1. The dogs had multiple episodes of aspiration pneumonia; dogs 1 and 2 were euthanatized at 84 and 93 months of age, respectively.
The clinical course of disease in these dogs was monitored for a longer period than has been monitored in previous reports of dystrophin-deficient dogs. The clinical progression of muscular dystrophy in the 2 GSHPs was compared with that for other breeds and species with dystrophin-deficient conditions, and the potential basis for the phenotypic variation observed between these littermates, along with potential therapeutic ramifications for dogs and humans, was evaluated.
Journal of the American Veterinary Medical Association 01/2011; 238(2):207-12. · 1.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: PRACTICAL RELEVANCE: Weakness is recognized somewhat infrequently in cats, but is an important manifestation of neurological disease. The clinician must perform a complete neurological examination to determine the neuroanatomic basis for the weakness. As for all species, the neuroanatomic diagnosis allows the clinician to generate an appropriate differential diagnosis, to design a diagnostic plan, to prognosticate, and ultimately to develop a treatment plan. CLINICAL CHALLENGES: The cause(s) of neurological weakness in the cat may be difficult to determine without access to advanced imaging modalities, cerebrospinal fluid analysis or electrodiagnostics. However, an accurate neuroanatomic diagnosis allows the clinician to pursue preliminary anomalous (vertebral anomalies), metabolic (eg, diabetes mellitus, electrolyte abnormalities) and neoplastic differentials via blood work, vertebral column and thoracic radiography, and abdominal ultrasound. Subsequently, referral to a specialty veterinary hospital may be warranted to pursue advanced neurodiagnostics. AUDIENCE: This review provides a framework for generating a neuroanatomic and differential diagnosis in the weak cat. It also discusses the pathogenesis and clinical signs associated with the most common neurological differentials for feline paresis. As such, it is aimed at both primary health care and specialty veterinarians. PATIENT GROUP: The neurological conditions discussed in this review cause weakness in cats of all age groups.
Journal of Feline Medicine & Surgery 06/2009; 11(5):373-83. · 1.08 Impact Factor