New Therapeutic approaches to Inclusion Body Myositis
Lead Research Organisation:
Medical Research Council
Department Name: Medical Research Council
Abstract
Inclusion Body Mysositis is the most common acquired muscle disease affecting people over 50 years old and is characterized by muscle weakness and degeneration, as well as chronic muscle inflammation. IBM affects 35 people in every million in the population over the age of 50 years. There is currently no effective treatment.
Developing new drugs for degenerative diseases is made much quicker when cell-based or invertebrate models are available. We have a simple nematode worm that has been genetically altered to mimic IBM. The diseased worms are noticeably less active than unaffected worms, which allows them to be distinguished from healthy ones. We already have a rapid working assay in place for this study and will develop an upscaled method for screening the actions of large numbers of compounds on these modified worms, to identify those which reverse the effects of IBM. This will not only provide new leads for drugs for treating IBM, but will also provide a method for screening large numbers of compounds that can be used in this and other applications. The most promising compounds will be tested on a human muscle cell line.
Developing new drugs for degenerative diseases is made much quicker when cell-based or invertebrate models are available. We have a simple nematode worm that has been genetically altered to mimic IBM. The diseased worms are noticeably less active than unaffected worms, which allows them to be distinguished from healthy ones. We already have a rapid working assay in place for this study and will develop an upscaled method for screening the actions of large numbers of compounds on these modified worms, to identify those which reverse the effects of IBM. This will not only provide new leads for drugs for treating IBM, but will also provide a method for screening large numbers of compounds that can be used in this and other applications. The most promising compounds will be tested on a human muscle cell line.
Technical Summary
Inclusion Body Mysositis is the most common acquired muscle disease affecting people over 50 years old and is characterized by muscle weakness and degeneration, as well as chronic muscle inflammation. IBM affects 35 people in every million in the population over the age of 50 years. There is currently no effective treatment. We will exploit an existing invertebrate model of IBM to screen a large library of novel compounds to identify possible new routes to therapy.
Oxford and UCL will collaborate with Senexis to develop models for the rapid assay of potential treatments for IBM. Oxford has a Caenorhabditis elegans model of IBM in which beta-amyloid is overexpressed in the muscle under the control of a heat-shock promoter. Induction of Abeta expression results in accumulation of amyloid deposits in the somatic muscles accompanied with paralysis and shortened lifespan. Oxford will develop a high-throughput assay for compounds that rescue the Abeta-induced paralysis. This will ensure that any increase in compound numbers can be accommodated. The results will be validated using an established human myoblast cell line.
UCL has expertise in cell line models of amyloid disease which will be used in parallel with the C. elegans models to screen Senexis compounds and to validate their action on a human model.
Oxford and UCL will collaborate with Senexis to develop models for the rapid assay of potential treatments for IBM. Oxford has a Caenorhabditis elegans model of IBM in which beta-amyloid is overexpressed in the muscle under the control of a heat-shock promoter. Induction of Abeta expression results in accumulation of amyloid deposits in the somatic muscles accompanied with paralysis and shortened lifespan. Oxford will develop a high-throughput assay for compounds that rescue the Abeta-induced paralysis. This will ensure that any increase in compound numbers can be accommodated. The results will be validated using an established human myoblast cell line.
UCL has expertise in cell line models of amyloid disease which will be used in parallel with the C. elegans models to screen Senexis compounds and to validate their action on a human model.