Targeted Macrophage Modulation as a Disease-Modifying Approach in Canine Osteoarthritis: The Efficacy of EF-M2 (ImmutalonTM) in a Double-Blind Placebo-Controlled Study. / Pokushalov, Evgeny; Kudlay, Dmitry; Revkov, Nikolai et al.
In: Veterinary Sciences, Vol. 12, No. 9, 919, 22.09.2025.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Targeted Macrophage Modulation as a Disease-Modifying Approach in Canine Osteoarthritis: The Efficacy of EF-M2 (ImmutalonTM) in a Double-Blind Placebo-Controlled Study
AU - Pokushalov, Evgeny
AU - Kudlay, Dmitry
AU - Revkov, Nikolai
AU - Shcherbakova, Anastasya
AU - Johnson, Michael
AU - Miller, Richard
N1 - This research was supported by an unrestricted research grant from Activator MAF, LLC, Novosibirsk, Russian Federation, and by internal funds of the Scientific Research Laboratory, Triangel Scientific (San Francisco, USA). The sponsor had no role in the study design; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Targeted Macrophage Modulation as a Disease-Modifying Approach in Canine Osteoarthritis: The Efficacy of EF-M2 (ImmutalonTM) in a Double-Blind Placebo-Controlled Study / E. Pokushalov, D. Kudlay, N. Revkov, A. Shcherbakova, M. Johnson, R. Miller // Veterinary Sciences. - 2025. - Т. 12. № 9. - С. 919. DOI 10.3390/vetsci12090919
PY - 2025/9/22
Y1 - 2025/9/22
N2 - Osteoarthritis is a prevalent and disabling condition in companion dogs, yet existing treatments are primarily symptomatic and limited by safety concerns. EF-M2, a defined derivative of vitamin D-binding protein, selectively biases macrophages toward an anti-inflammatory phenotype in vitro. We conducted a randomised, double-blind, placebo-controlled trial (IMPAWS-OA-1) in 60 client-owned dogs with naturally occurring hip or elbow osteoarthritis. Animals were allocated to subcutaneous EF-M2 (0.1 µg/kg) given thrice weekly or twice weekly, or to saline placebo for four weeks, followed by four weeks off-drug. The primary endpoint was change in Canine Brief Pain Inventory–Pain Severity Score (CBPI-PSS) at Day 28. EF-M2 produced dose–frequency-dependent benefits: LS-mean ΔPSS was −2.11 for thrice weekly, −1.42 for twice weekly, and −0.54 for placebo (arm effect p < 0.001). Objective measures showed parallel improvements in peak vertical force and accelerometery. Serum biomarkers confirmed macrophage repolarisation (ARG1/iNOS ratio, IL-10 increase, TNF-α decrease), correlating with clinical response. Adverse events were infrequent and mild, with no excess over placebo. In conclusion, EF-M2 achieved clinically meaningful pain relief, functional gains, and biomarker shifts without safety signals, establishing first-in-species proof that targeted macrophage modulation may be a viable disease-modifying approach for canine osteoarthritis.
AB - Osteoarthritis is a prevalent and disabling condition in companion dogs, yet existing treatments are primarily symptomatic and limited by safety concerns. EF-M2, a defined derivative of vitamin D-binding protein, selectively biases macrophages toward an anti-inflammatory phenotype in vitro. We conducted a randomised, double-blind, placebo-controlled trial (IMPAWS-OA-1) in 60 client-owned dogs with naturally occurring hip or elbow osteoarthritis. Animals were allocated to subcutaneous EF-M2 (0.1 µg/kg) given thrice weekly or twice weekly, or to saline placebo for four weeks, followed by four weeks off-drug. The primary endpoint was change in Canine Brief Pain Inventory–Pain Severity Score (CBPI-PSS) at Day 28. EF-M2 produced dose–frequency-dependent benefits: LS-mean ΔPSS was −2.11 for thrice weekly, −1.42 for twice weekly, and −0.54 for placebo (arm effect p < 0.001). Objective measures showed parallel improvements in peak vertical force and accelerometery. Serum biomarkers confirmed macrophage repolarisation (ARG1/iNOS ratio, IL-10 increase, TNF-α decrease), correlating with clinical response. Adverse events were infrequent and mild, with no excess over placebo. In conclusion, EF-M2 achieved clinically meaningful pain relief, functional gains, and biomarker shifts without safety signals, establishing first-in-species proof that targeted macrophage modulation may be a viable disease-modifying approach for canine osteoarthritis.
KW - ARG1/iNOS
KW - CLEC10A
KW - Canine Brief Pain Inventory
KW - GcMAF
KW - IL-10
KW - TNF-α
KW - accelerometry
KW - degenerative joint disease
KW - dogs
KW - macrophage polarization
KW - peak vertical force
KW - dogs
KW - degenerative joint disease
KW - macrophage polarization
KW - CLEC10A
KW - GcMAF
KW - peak vertical force
KW - accelerometry
KW - Canine Brief Pain Inventory
KW - ARG1/iNOS
KW - IL-10
KW - TNF-α
UR - https://www.mendeley.com/catalogue/d11de766-0f66-3cdd-be33-8c50a5487d74/
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105017077575&origin=inward
UR - https://pubmed.ncbi.nlm.nih.gov/41012844/
U2 - 10.3390/vetsci12090919
DO - 10.3390/vetsci12090919
M3 - Article
C2 - 41012844
VL - 12
JO - Veterinary Sciences
JF - Veterinary Sciences
SN - 2306-7381
IS - 9
M1 - 919
ER -
ID: 70117938