Transcriptome Profiling of Canine Familial Dermatomyositis (DMS) Skin Lesions and Treatment
Cutaneous dermatomyositis (DMS) is a chronic immune-mediated disease that exhibits severe inflammatory lesions leading to skin scarring with disfiguration. The inflammatory skin process in human DMS is characterized by an upregulated interferon signature and activation of Janus kinase (JAK) pathway; the JAK inhibitors represent a novel treatment modality for human cutaneous DMS. Presently, little is known about the pathogenesis of canine familial DMS-associated skin lesions in Collies and Shetland Sheepdogs and the treatment is rarely successful. Oclacitinib is safe and well-tolerated JAK inhibitor that has been used for the control or treatment of allergic dermatitis in dogs; however, the therapeutic effect of oclacitinib on canine familial DMS has not been investigated.
The primary objective of this study is to evaluate the molecular signature of canine familial DMS using RNA sequencing. We will perform transcriptomic analyses of lesional skin biopsy specimens from 20 dogs (Collies, Shetland Sheepdogs) with familial DMS; biopsy specimens from 10 healthy dogs will serve as a control. Alignment of RNA-seq reads and detailed comparative analysis will be identified using software services. Furthermore, we will evaluate the effect of oclacitinib, a veterinary JAK inhibitor, on the modulation of the cutaneous DMS clinical signs in dogs in a 12-week open-label study. This is the first evaluation of a targeted immune JAK antagonist in dogs with familial DMS. The robust transcriptome analysis using RNA-seq will define novel pathogenic (innate, adaptive and inflammatory) pathways canine DMS disease drivers, with potential for the development of new targeted therapeutics.
Client-owned Collies and Shetland Sheepdogs of any age, body weight and sex, with active cutaneous DMS diagnosed based on currently accepted standards (i.e. compatible history, clinical signs and microscopic demonstration of cell-poor interface dermatitis with vasculopathy, follicular atrophy and fibrosis on previous skin biopsy) will be enrolled into the study.
To limit the influence of medications on active DMS skin lesions, withdrawal times for all dogs from previous medications will be as follows: 2 weeks for oral pentoxifylline, topical (skin and ear) and oral glucocorticoids, 4 weeks for cyclosporine, oclacitinib and other immunomodulators (e.g. azathioprine, mycophenolate mofetil, leflunomide etc) and 8 weeks for injectable glucocorticoids.
Once the patient is accepted into the study, the primary investigator will be in contact with the clients to organize a one-time skin biopsy collection procedure at a veterinary dermatologist clinic or a primary veterinarian clinic. The primary investigator is responsible for the shipments of all materials. Samples can be sent from other clinics/owners.
If the clients pursue treatment with oclacitinib, the primary investigator will contact the clients directly with clinical scoring materials and the client will be responsible to bring the patient for a clinical visit rechecks to a veterinary dermatologist or a primary veterinarian.
Name: Frane Banovic, DVM, PhD
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Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.