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

IF 2.3 2区 农林科学 Q2 VETERINARY SCIENCES
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}
引用次数: 0

摘要

骨关节炎是伴侣犬的一种普遍致残疾病,但现有的治疗主要是症状性的,并且受到安全问题的限制。EF-M2是一种维生素d结合蛋白的衍生物,在体外实验中选择性地使巨噬细胞倾向于抗炎表型。我们进行了一项随机、双盲、安慰剂对照试验(IMPAWS-OA-1),在60只客户拥有的患有自然发生的髋关节或肘部骨关节炎的狗中进行。动物被分配给皮下注射EF-M2(0.1µg/kg),每周3次或每周2次,或生理盐水安慰剂4周,随后4周停药。主要终点是第28天犬短暂疼痛量表-疼痛严重程度评分(CBPI-PSS)的变化。EF-M2产生剂量频率依赖的益处:每周三次的ls平均ΔPSS为-2.11,每周两次为-1.42,安慰剂为-0.54(臂效应p < 0.001)。客观测量显示峰值垂直力和加速度计平行改善。血清生物标志物证实巨噬细胞重极化(ARG1/iNOS比值、IL-10升高、TNF-α降低),与临床反应相关。不良事件很少且轻微,没有超过安慰剂。综上所述,EF-M2在没有安全信号的情况下实现了临床意义上的疼痛缓解、功能增益和生物标志物转移,首次在物种中证明靶向巨噬细胞调节可能是治疗犬骨关节炎的一种可行的疾病改善方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Veterinary Sciences
Veterinary Sciences VETERINARY SCIENCES-
CiteScore
2.90
自引率
8.30%
发文量
612
审稿时长
6 weeks
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信