Efficacy of p62-expressing plasmid in treatment of canine osteoarthritis.

Introduction: Osteoarthritis (OA) is a progressive degenerative disease of synovial joints which is highly prevalent in dogs and results in lameness, loss of joint function and mobility, chronic pain, and reduced quality of life. Traditional OA management consist of non-steroidal anti-inflammatory drugs and remains challenging because of significant side effects, thus there is an urgent need for new effective and safe therapeutics for OA. Methods: Here we present the results of our one-arm open-label pilot clinical study of our novel biologics, a DNA plasmid encoding SQSTM/p62, in 17 companion dogs suffering from OA. The dogs were injected intramuscular with p62-plasmid once a week for 10 weeks, and pain relief was measured using the CBPI (canine brief pain inventory) validated scale. Assessment by the owners was done weekly. The 11 parameters of CBPI are grouped in three major domains: pain severity score (PSS), pain interference score (PIS) and overall impression of the quality of life (QoL). Results: Treatment with the p62-plasmid improved all 11 parameters of CBPI as well as PSS, PIS and QoL: mean PSS score after the treatment decreased from 5.25 to 3.25, PIS score - from 7.0 to 3.27, and number of dogs with excellent and good QoL due to treatment increased from 1 to 12. Overall, the treatment success rate (i.e. a reduction ≥1 in PSS and ≥ 2 in PIS) was 90%. Importantly, similar to our previous studies with dogs and humans, no significant side effects of the p62-plasmid during the whole treatment period were observed. Discussion: We believe that anti-inflammatory effects of the p62-plasmid, which we described in our previous works, may play an important role in observed clinical benefits and it is worthy of further studies as a novel OA treatment modality.