TY - JOUR

T1 - Precision Glyco-Modulation of Macrophages with EF-M2 (ImmutalonTM) Improves Function and Lowers Inflammatory Biomarkers in Aging Dogs: A Double-Blind, Placebo-Controlled Trial

AU - Pokushalov, Evgeny

AU - Kudlay, Dmitry

AU - Garcia, Claire

AU - Smith, John

AU - Revkov, Nikolai

AU - Shcherbakova, Anastasya

AU - Miller, Richard

N1 - Precision Glyco-Modulation of Macrophages with EF-M2 (ImmutalonTM) Improves Function and Lowers Inflammatory Biomarkers in Aging Dogs: A Double-Blind, Placebo-Controlled Trial / E. Pokushalov, D. Kudlay, C. Garcia [et al.] // Veterinary Sciences. – 2025. – Vol. 12. - No. 12. – P. 1168. – DOI 10.3390/vetsci12121168. – EDN FDMRXC. 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 study design; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

PY - 2025/12/9

Y1 - 2025/12/9

N2 - We evaluated whether macrophage-targeted glyco-modulation can improve day-to-day function in aging companion animals. In a multicenter, randomized, double-blind, placebo-controlled trial, 60 client-owned geriatric dogs (≥10 years) received subcutaneous EF-M2 (0.1 μg/kg, every 72 h for 4 weeks; protocolized, blinded step-up to every 48 h at day 14 for partial responders) or matched placebo, followed by 4 weeks off-treatment. Two prespecified co-primary endpoints were tested hierarchically: change in accelerometer-measured active minutes/day at week 1 and change in a day-28 vitality composite (z-score of inverted CBPI-PSS, HRQL-vitality, and appetite VAS). EF-M2 was superior to placebo on both: +23.05 min/day at week 1 (95% CI, 18.16–27.94; p < 0.001) and +2.01 z-units at day 28 (95% CI, 1.52–2.50; p < 0.001). Key secondaries favored EF-M2, including greater week-4 activity (+33.00 min/day, 26.83–39.18; p < 0.001), lower BAER auditory threshold (−5.28 dB, −7.53 to −3.04; p < 0.001), and reduced transepidermal water loss (−1.35 g/m2·h, −2.45 to −0.25; p = 0.02); multiplicity was controlled with Holm–Bonferroni procedures. Owner-reported global improvement was more frequent with EF-M2 at day 28 (93.3% vs. 10.0%) and remained higher at day 56 off-treatment (50.0% vs. 16.7%). Prespecified pharmacodynamic markers shifted in directions consistent with M2-skewing (ARG1:iNOS ratio and IL-10 increased; TNF-α decreased) by day 7. Adverse events were infrequent, mild, and similar to placebo; no treatment-related withdrawals or serious events occurred. These findings support macrophage-targeted glyco-modulation as a promising approach to rapidly improve real-world activity and multidomain vitality in older dogs, with short-term signals persisting off-treatment; longer, adequately powered trials are warranted to define durability, structural outcomes, and phenotype-specific benefits.

AB - We evaluated whether macrophage-targeted glyco-modulation can improve day-to-day function in aging companion animals. In a multicenter, randomized, double-blind, placebo-controlled trial, 60 client-owned geriatric dogs (≥10 years) received subcutaneous EF-M2 (0.1 μg/kg, every 72 h for 4 weeks; protocolized, blinded step-up to every 48 h at day 14 for partial responders) or matched placebo, followed by 4 weeks off-treatment. Two prespecified co-primary endpoints were tested hierarchically: change in accelerometer-measured active minutes/day at week 1 and change in a day-28 vitality composite (z-score of inverted CBPI-PSS, HRQL-vitality, and appetite VAS). EF-M2 was superior to placebo on both: +23.05 min/day at week 1 (95% CI, 18.16–27.94; p < 0.001) and +2.01 z-units at day 28 (95% CI, 1.52–2.50; p < 0.001). Key secondaries favored EF-M2, including greater week-4 activity (+33.00 min/day, 26.83–39.18; p < 0.001), lower BAER auditory threshold (−5.28 dB, −7.53 to −3.04; p < 0.001), and reduced transepidermal water loss (−1.35 g/m2·h, −2.45 to −0.25; p = 0.02); multiplicity was controlled with Holm–Bonferroni procedures. Owner-reported global improvement was more frequent with EF-M2 at day 28 (93.3% vs. 10.0%) and remained higher at day 56 off-treatment (50.0% vs. 16.7%). Prespecified pharmacodynamic markers shifted in directions consistent with M2-skewing (ARG1:iNOS ratio and IL-10 increased; TNF-α decreased) by day 7. Adverse events were infrequent, mild, and similar to placebo; no treatment-related withdrawals or serious events occurred. These findings support macrophage-targeted glyco-modulation as a promising approach to rapidly improve real-world activity and multidomain vitality in older dogs, with short-term signals persisting off-treatment; longer, adequately powered trials are warranted to define durability, structural outcomes, and phenotype-specific benefits.

KW - CLEC10A

KW - EF-M2 (GcMAF derivative)

KW - geriatric dogs

KW - inflammaging

KW - low-grade inflammation

KW - macrophage modulation

UR - https://www.scopus.com/pages/publications/105025659144

UR - https://elibrary.ru/item.asp?id=88117611

UR - https://www.mendeley.com/catalogue/afa2f4c9-7dc4-3d2b-81e4-e54e415ea494/

U2 - 10.3390/vetsci12121168

DO - 10.3390/vetsci12121168

M3 - Article

VL - 12

JO - Veterinary Sciences

JF - Veterinary Sciences

SN - 2306-7381

IS - 12

M1 - 1168

ER -