02921-MOU: Transcriptome Profiling of Canine Familial Dermatomyositis Skin Lesions and Treatment with a JAK Inhibitor to Identify Novel Pathways Involved in Pathogenesis
Grant Status: Open
One Health: Yes
Abstract
Dermatomyositis (DMS) is a chronic inflammatory and autoimmune disorder affecting primarily skin and muscle in both humans and dogs. Familial canine DMS is mainly described in predisposed breeds, such as Collies and Shetland Sheepdogs, and is characterized by severe inflammatory lesions leading to skin scarring with disfiguration, increased morbidity and decreased quality of life. Full clinical remission of DMS skin lesions can be difficult to achieve, reflecting a poor understanding of the pathogenesis of skin lesions in this disease. The transcriptome (gene expression analysis) investigation of human DMS tissues has revolutionized the understanding of the molecular fingerprint of DMS, further defining pathogenic immune pathways and identifying disease-specific biomarkers. Recently, a novel mechanism-based treatment using Janus kinase (JAK) inhibitors has led to a significant clinical and molecular improvement in refractory cutaneous DMS in humans. Oclacitinib is a safe and well-tolerated JAK inhibitor that has been used for the treatment of allergic dermatitis in dogs; however, the therapeutic effect of oclacitinib on canine immune-mediated diseases, such as DMS, has not been investigated. The main objective of this study is to perform a large-scale molecular signature analysis of canine familial DMS. Investigators hypothesize that integrating deep sequencing-based transcriptome profiling with systems biology analysis will identify novel pathogenic pathways and inflammatory biomarkers as canine DMS disease drivers, with potential for the development of novel targeted therapeutics. Furthermore, they will evaluate the effect of oclacitinib, a novel veterinary JAK inhibitor, on the modulation of the cutaneous DMS clinical signs in dogs. These results may suggest that JAK inhibition has the potential to reverse canine DMS pathomechanisms, opening the door to a new era of targeted treatment for this debilitating inflammatory skin disease.
Funding for the research is provided through the collaborative efforts and generosity of the Collie Health Foundation and American Shetland Sheepdog Association. The AKC Canine Health Foundation supports the funding of this effort and will oversee grant administration and scientific progress.
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