Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2024 Nov 21:rs.3.rs-5461004.
doi: 10.21203/rs.3.rs-5461004/v1.

Efficacy of p62-expressing plasmid in treatment of canine osteoarthritis

Vladimir Gabai  1 , Evgeny Bakin  2 , Maxim Harold Langs  3 , Robert Delvin  4 , Sergei Krasny  5 , Yauheni Baranau  6 , Sergey Polyakov  7 , Maksim Patapovich  8 , Sergey Gvozdev  9 , Maksim Kardash  10 , Aliaksei Bazyleuski  11 , Andrei Yeliseyeu  12 , Egor Lelikov  13 , Andrei Barodka  14 , Alexander Shneider  15
Affiliations

Efficacy of p62-expressing plasmid in treatment of canine osteoarthritis

Vladimir Gabai et al. Res Sq. .

Update in

Abstract

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.

Keywords: DNA vaccine; chronic pain; clinical trial; inflammation; safety.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Changes in PIS and PSS scores after the treatment with p62 plasmid (described with a median, Q1 and Q3).
Figure 2
Figure 2
CBPI score dynamics during the treatment with p62 plasmid
Figure 3
Figure 3
Spearman correlation ρ for each parameter of subjective assessment (CBPI score). See Materials and Methods for details.
See this image and copyright information in PMC

References

    1. Anderson KL, O’Neill DG, Brodbelt DC, Church DB, Meeson RL, Sargan D et al. (2018) Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care. Sci Rep 8(1):5641. - PMC - PubMed
    1. Henrotin Y, Sanchez C, Balligand M (2005) Pharmaceutical and nutraceutical management of canine osteoarthritis: present and future perspectives. Vet J 170(1):113–123 - PubMed
    1. Lee AS, Ellman MB, Yan D, Kroin JS, Cole BJ, van Wijnen AJ et al. (2013) A current review of molecular mechanisms regarding osteoarthritis and pain. Gene 527(2):440–447 - PMC - PubMed
    1. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J-P, Fahmi H (2011) Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 7(1):33–42 - PubMed
    1. Fernandes JC, Martel-Pelletier J, Pelletier JP (2002) The role of cytokines in osteoarthritis pathophysiology. Biorheology 39(1–2):237–246 - PubMed

Publication types

LinkOut - more resources