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 -