Evgeny Pokushalov, Dmitry Kudlay, Nikolai Revkov, Anastasya Shcherbakova, Michael Johnson, Richard Miller
{"title":"靶向巨噬细胞调节作为犬骨关节炎的疾病改善途径:EF-M2 (ImmutalonTM)在一项双盲安慰剂对照研究中的疗效","authors":"Evgeny Pokushalov, Dmitry Kudlay, Nikolai Revkov, Anastasya Shcherbakova, Michael Johnson, Richard Miller","doi":"10.3390/vetsci12090919","DOIUrl":null,"url":null,"abstract":"<p><p>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 <i>p</i> < 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.</p>","PeriodicalId":23694,"journal":{"name":"Veterinary Sciences","volume":"12 9","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474438/pdf/","citationCount":"0","resultStr":"{\"title\":\"Targeted Macrophage Modulation as a Disease-Modifying Approach in Canine Osteoarthritis: The Efficacy of EF-M2 (Immutalon<sup>TM</sup>) in a Double-Blind Placebo-Controlled Study.\",\"authors\":\"Evgeny Pokushalov, Dmitry Kudlay, Nikolai Revkov, Anastasya Shcherbakova, Michael Johnson, Richard Miller\",\"doi\":\"10.3390/vetsci12090919\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 <i>p</i> < 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.</p>\",\"PeriodicalId\":23694,\"journal\":{\"name\":\"Veterinary Sciences\",\"volume\":\"12 9\",\"pages\":\"\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474438/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Veterinary Sciences\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.3390/vetsci12090919\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary Sciences","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.3390/vetsci12090919","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
Targeted Macrophage Modulation as a Disease-Modifying Approach in Canine Osteoarthritis: The Efficacy of EF-M2 (ImmutalonTM) in a Double-Blind Placebo-Controlled Study.
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.
期刊介绍:
Veterinary Sciences is an international and interdisciplinary scholarly open access journal. It publishes original that are relevant to any field of veterinary sciences, including prevention, diagnosis and treatment of disease, disorder and injury in animals. This journal covers almost all topics related to animal health and veterinary medicine. Research fields of interest include but are not limited to: anaesthesiology anatomy bacteriology biochemistry cardiology dentistry dermatology embryology endocrinology epidemiology genetics histology immunology microbiology molecular biology mycology neurobiology oncology ophthalmology parasitology pathology pharmacology physiology radiology surgery theriogenology toxicology virology.