title: Validity of a Neurological Scoring System for Canine X-Linked Myotubular Myopathy.
abstract: A simple clinical neurological test was developed to evaluate response to gene therapy in a preclinical canine model of X-linked myotubular myopathy (XLMTM). This devastating congenital myopathy is caused by mutation in the myotubularin (MTM1) gene. Clinical signs include muscle weakness, early respiratory failure, and ventilator dependence. A spontaneously occurring canine model has a similar clinical picture and histological abnormalities on muscle biopsy compared with patients. We developed a neuromuscular assessment score, graded on a scale from 10 (normal) to 1 (unable to maintain sternal recumbency). We hypothesize that this neurological assessment score correlates with genotype and established measures of disease severity and is reliable when performed by an independent observer. At 17 weeks of age, there was strong correlation between neurological assessment scores and established methods of severity testing. The neurological severity score correctly differentiated between XLMTM and wild-type dogs with good interobserver reliability, on the basis of strong agreement between neurological scores assigned by independent observers. Together, these data indicate that the neurological scoring system developed for this canine congenital neuromuscular disorder is reliable and valid. This scoring system may be helpful in evaluating response to therapy in preclinical testing in this disease model, such as response to gene therapy.
authors.affiliation: 1 Department of Comparative Medicine, University of Washington , Seattle, WA 98195.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Snyder
authors.affiliation: 2 Department of Biostatistics, University of Washington , Seattle, WA 98195.
authors.forename: Allison
authors.initials: A
authors.lastname: Meisner
authors.affiliation: 3 Department of Rehabilitation Medicine, University of Washington , Seattle, WA 98195.|4 Institute for Stem Cell and Regenerative Medicine, School of Medicine, University of Washington , Seattle, WA 98195.
authors.forename: David
authors.initials: D
authors.lastname: Mack
authors.affiliation: 4 Institute for Stem Cell and Regenerative Medicine, School of Medicine, University of Washington , Seattle, WA 98195.|5 Department of Integrative Physiology and Pharmacology, Wake Forest University , Winston Salem, NC 27101.
authors.forename: Melissa
authors.initials: M
authors.lastname: Goddard
authors.affiliation: 4 Institute for Stem Cell and Regenerative Medicine, School of Medicine, University of Washington , Seattle, WA 98195.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Coulter
authors.affiliation: 6 Department of Human Nutrition, Foods and Exercise, Virginia Tech University , Blacksburg, VA 24061.
authors.forename: Robert
authors.initials: R
authors.lastname: Grange
authors.affiliation: 3 Department of Rehabilitation Medicine, University of Washington , Seattle, WA 98195.|4 Institute for Stem Cell and Regenerative Medicine, School of Medicine, University of Washington , Seattle, WA 98195.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Childers
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005684:Gait; D015316:Genetic Therapy; D018908:Muscle Weakness; D020914:Myopathies, Structural, Congenital / Q000503:physiopathology* / Q000628:therapy*; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*; D015203:Reproducibility of Results; D012720:Severity of Illness Index
chemical_list: D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin