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Abstract Number: 1726

Therapeutic Effect of ICAM-1 Mimic on Experimental Axial Spondyloarthritis

Melissa Lim1, Shaghayegh Foroozan2, Zoya Qaiyum3, Michael Tang1, Enoch Yau4 and Robert Inman1, 1University Health Network, Toronto, ON, Canada, 2University Health Network/University of Toronto, Toronto, ON, Canada, 3Krembil Research Institute, Toronto, ON, Canada, 4University of Toronto, Toronto, ON, Canada

Meeting: ACR Convergence 2023

Keywords: Animal Model, Ankylosing spondylitis (AS), cytokines, immunology, Mouse Models, RA

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Session Information

Date: Tuesday, November 14, 2023

Title: (1713–1733) RA – Animal Models Poster

Session Type: Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Axial Spondyloarthritis (AxSpA) is a chronic inflammatory arthritis primarily affecting the axial skeleton and commonly coexists with gut and skin inflammation. Currently, patients with axSpA require lifelong treatment. Current biologics (TNFi, IL-17i, JAKi)improve symptoms but are not curative and cannot prevent disease progression.

With the help of AI technology highlighting several unique small molecules with the potential efficacy in axSpA, it was possible to identify a potential small molecule that acts on the binding site of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1). The LFA-1/ICAM-1 interaction is known to enable both T-cell activation and pro-inflammatory cytokine release. Through previously associated work with computational science and a preclinical in vivo model using DBA/1 collagen induced arthritis model, we have seen significant effects, resulting in decreased arthritis score and paw thickness. It is with this ICAM-1-mimicing small molecule compound that this study reports on the effect blocking this interaction has on an axSpA murine model.

Methods: We employed the use of the SKG mouse, an IL-23- and IL17-dependent model leading to disease resembling human axSpA. SKG mice given a single dose 3mg curdlan (intraperitoneal) developed skin inflammation in ears and tail, blepharitis, and swelling of ankles and wrists and digits. Therapeutic intervention began one week post-curdlan disease induction. These mice were treated with varying doses of the ICAM-1 mimic via daily intraperitoneal (IP) injections and monitored for 8weeks.

Results: With the SKG mice, theICAM-1 mimic showed excellent tolerability and showed a significant decrease in clinical scores, which was most pronounced in the low dose treatment group (G3 in Fig 1). Histological analysis with H&E staining indicated that animals treated with the compound had significantly reduced histological scores of tails, skin, ankle, and gut for the low dose treatment group (G3).

Conclusion: This small molecule ICAM-1 mimic, identified by an axSpA drug discovery approach, shows efficacy in this preclinical model. Follow-up studies will examine pharmacokinetics and pharmacodynamics of the compound. This is promising data for application of this ICAM-1 mimic as a new therapeutic option for axSpA.

Supporting image 1

Breakdown of the treatment groups of the SKG mice for the experiment. Three different treatment doses were examined, along with control groups (healthy, diseased, dexamethasone-treated)

Supporting image 2

Clinical scores of the treatment groups with significance seen between the disease group (G2) and low dose (G3) treatment group.

Supporting image 3

Histological analysis H&E staining of joints. Left panel shows the ankle scores with significance seen between the disease (G2) and low dose (G3) groups. Right panel shows the ankle score with significance seen between the same two groups.


Disclosures: M. Lim: Aria Pharmaceuticals, 5; S. Foroozan: None; Z. Qaiyum: None; M. Tang: None; E. Yau: None; R. Inman: AbbVie, 2, Eli Lilly, 2, Janssen, 2, Novartis, 2, Sandoz, 2.

To cite this abstract in AMA style:

Lim M, Foroozan S, Qaiyum Z, Tang M, Yau E, Inman R. Therapeutic Effect of ICAM-1 Mimic on Experimental Axial Spondyloarthritis [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/therapeutic-effect-of-icam-1-mimic-on-experimental-axial-spondyloarthritis/. Accessed .
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