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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.