Testing small interfering RNA therapeutics for inflammatory skin conditions in companion dogs

The purpose of this study is to evaluate the effectiveness of a new therapy for two different skin diseases in dogs: atopic dermatitis and cutaneous lupus. These conditions are usually treated with drugs that are given systemically (orally or by injection under the skin). Sometimes these systemic treatments can have side effects. In the current study, a local injection of a new type of treatment called an siRNA will be used to target a key protein in immune cells called JAK1 which is known to be involved in both atopic dermatitis and cutaneous lupus. This siRNA works by causing the JAK1 protein to be broken down, which then interferes with the ability of the immune cells causing disease to survive. Because the siRNA is being injected directly into the affected skin areas, it does not affect JAK1 in other parts of the body. This JAK1 siRNA has been tested in mouse models and has been found to be safe and to work in the setting of experimentally induced skin disease.

Inclusion Criteria

• At least 6 months of age
• Weighs 5 kg (11 pounds) or greater
• No significant underlying illness based on physical examination and CBC, serum chemistry and urinalysis
• Confirmed chronic inflammatory noncommunicable skin disease for more than 3 months

Exclusion Criteria

• Pregnancy
• Within 2 weeks of oral or topical and one month of injectable global immunosuppressive treatments
• Evidence of systemic comorbidities such as cancer, endocrinopathies, liver or kidney disease or urinary/respiratory tract infections

Client Benefits

The study covers all costs associated with the procedures involved except the routine bloodwork at the study visits indicated in the calendar below (CBC and chemistry panel and urinalysis). The estimated cost for these tests is $250 on the screening visit, Week 4 and Week 12. Side effects related to the drug treatment will be covered by the study. If your dog’s skin continues to improve, then monthly JAK1 siRNA will be administered for another 8 months; while the JAK siRNA will be provided for free, the other visit costs will be your responsibility (estimated at $200-$250 per visit). However, treatment of other conditions (bladder infection, ear infection, etc.) is not covered by the study. Treatment beyond the planned the final visit will not be covered by the study.

Sample or Data Requirements

If your dog is deemed eligible for enrollment based on screening physical exam and bloodwork (diagnosis of atopic dermatitis or cutaneous lupus, eating/drinking normally and free of any other serious conditions such as heart/kidney/ liver disease), your dog will first undergo study blood collection and a punch biopsy (6-8mm punch diameter) of the affected skin. Your dog will then undergo local intradermal (in the skin) injections (up to 10 different affected body sites) of the JAK1 siRNA into affected skin areas once per month for a total of 5 injections (at the first day of inclusion in the study and for four months thereafter). Blood (approximately 1 tablespoon) will be collected at 6 different visits to check cell counts and organ function, as well as for study purposes. At Week 6 of the study, a second punch biopsy will be taken. If your dog’s skin is improving, then the monthly JAK1 siRNA will be continued, and a third punch biopsy will be taken at Week 12 of the study. The final study visit and JAK1 siRNA injection will occur at Week 16. If at that time your dog is still experiencing benefit from the treatment, then the JAK1 siRNA injections can be continued for another 8 months on a compassionate use basis.

Contact

For questions regarding the clinical trial, please email clinicaltrials@tufts.edu.