PUBLICATION
Testing of therapies in a novel nebulin nemaline myopathy model demonstrate a lack of efficacy
- Authors
- Sztal, T.E., McKaige, E.A., Williams, C., Oorschot, V., Ramm, G., Bryson-Richardson, R.J.
- ID
- ZDB-PUB-180601-1
- Date
- 2018
- Source
- Acta neuropathologica communications 6: 40 (Journal)
- Registered Authors
- Bryson-Richardson, Robert, Sztal, Tamar Esther
- Keywords
- Nebulin, Nemaline myopathy, Treatment, Zebrafish
- MeSH Terms
-
- Actins/metabolism
- Animals
- Animals, Genetically Modified
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian
- Gene Expression Regulation/genetics
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Microfilament Proteins/genetics
- Microfilament Proteins/metabolism
- Microscopy, Electron
- Muscle Proteins/genetics
- Muscle Proteins/metabolism*
- Muscle Proteins/therapeutic use*
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/pathology*
- Muscle, Skeletal/ultrastructure
- Mutation/genetics*
- Myopathies, Nemaline/genetics
- Myopathies, Nemaline/pathology*
- Myopathies, Nemaline/therapy*
- RNA, Messenger/metabolism
- Zebrafish
- PubMed
- 29848386 Full text @ Acta Neuropathol Commun
Citation
Sztal, T.E., McKaige, E.A., Williams, C., Oorschot, V., Ramm, G., Bryson-Richardson, R.J. (2018) Testing of therapies in a novel nebulin nemaline myopathy model demonstrate a lack of efficacy. Acta neuropathologica communications. 6:40.
Abstract
Nemaline myopathies are heterogeneous congenital muscle disorders causing skeletal muscle weakness and, in some cases, death soon after birth. Mutations in nebulin, encoding a large sarcomeric protein required for thin filament function, are responsible for approximately 50% of nemaline myopathy cases. Despite the severity of the disease there is no effective treatment for nemaline myopathy with limited research to develop potential therapies. Several supplements, including L-tyrosine, have been suggested to be beneficial and consequently self-administered by nemaline myopathy patients without any knowledge of their efficacy. We have characterized a zebrafish model for nemaline myopathy caused by a mutation in nebulin. These fish form electron-dense nemaline bodies and display reduced muscle function akin to the phenotypes observed in nemaline myopathy patients. We have utilized our zebrafish model to test and evaluate four treatments currently self-administered by nemaline myopathy patients to determine their ability to increase skeletal muscle function. Analysis of muscle pathology and locomotion following treatment with L-tyrosine, L-carnitine, taurine, or creatine revealed no significant improvement in skeletal muscle function emphasizing the urgency to develop effective therapies for nemaline myopathy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping