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XBiotech Announces First Patient in Clinical Study to Evaluate Bermekimab in Systemic Sclerosis
SSc is characterized by systemic inflammation that results in injury to blood vessels, and fibrosis of the skin and internal organs1. Skin lesions can be severe, resulting in disfiguration and debilitating pain. In addition, patients suffering from SSc have substantially reduced life expectancy due to the fibrosis that occurs in vital organs and chronic inflammation of the blood vessels2.
While the cause of SSc is unknown, pathogenesis of the disease is understood to involve errant activation of fibroblasts. In normal organs and tissues, fibroblast cells play a crucial role in building the structural framework of connective tissue that holds the organs and tissues together. Fibroblasts produce the extracellular matrix substances that actually enable the organ structure. When fibroblasts are errantly activated in SSc, they become hyperactive and produce excessive extracellular matrix, which is the basis for fibrosis.
An initial step in the SSc disease process is believed to be the release of the potent inflammatory cytokine interleukin-1 alpha (IL-1⍺) from keratinocytes in the epidermis3. The release of IL-1⍺ results in the production of a myriad of other inflammatory cytokines, including IL-6, TNF, IL-8, IL-10, and others from surrounding tissues4,5,6,7. Blocking IL-1⍺ could abrogate the pathological cascade that occurs in this disease. Bermekimab specifically binds and neutralizes IL-1⍺.
Errant IL-1⍺ production has been repeatedly shown to occur in cells of patients with SSc (8,9). IL-1⍺ levels are elevated in SSc patients10,11, including in the skin and in lung fluids of SSc patients with pulmonary fibrosis; and when IL-1⍺ production is induced in normal fibroblasts, these take on the characteristics of SSc fibroblasts12.
Evangelos Giamarellos-Bourboulis, MD, PhD, Professor of Internal Medicine,
The most common affected organs in SSc are the skin, the gastrointestinal tract, the lungs, and the heart. Capillary endothelium is involved, leading to ischemia and digital necrosis. Patients develop an interstitial lung disease (ILD) prototype dominated by pulmonary hypertension (PHA) and failed gas exchange. Almost all patients also have signs of intestinal dysmotility leading to gastrointestinal reflux and bloating13. Hallmarks of SSc are fibrosis of the skin and internal organs and vasculopathy. SSc is the only rheumatic disorder accompanied by substantial lethality; so far no specific treatment targeting the mechanism of pathogenesis is available.
About True Human™ Therapeutic Antibodies
XBiotech’s True Human™ antibodies are derived without modification from individuals who possess natural immunity to certain diseases. With discovery and clinical programs across multiple disease areas, XBiotech’s True Human antibodies have the potential to harness the body’s natural immunity to fight disease with increased safety, efficacy and tolerability.
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1 Varga J, Abraham D (2007) Systemic sclerosis. A prototypic multisystem fibrotic disorder. J Clin Invest 117:557–67.
2 Steen VD, Medsger TA Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 2000; 43: 2437–2444.
3 Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions inwound healing. J Invest Dermatol 2007; 127: 998 1008.
4 Engelhardt E, Toksoy A, Goebeler M, Debus S, Bröcker EB, Gillitzer R. Chemokines IL-8, GROa, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. Am J Pathol 1998; 153: 1849–1860.
5 Uchi H, Terao H, Koga T, Furue M. Cytokines and chemokines in the epidermis. J Invest Dermatol 2000; 24S: 529-538.
6 Gillitzer R, Goebeler M. Chemokines in cutaneous wound healing. J Leukoc Biol 2001; 69: 513–521.
7 Gillitzer R, Goebeler M. Chemokines in cutaneous wound healing. J Leukoc Biol 2001; 69: 513–521.
8 Kawaguchi Y, Hara M, Wright TM. Endogenous IL-1a from systemic sclerosis fibroblasts induces IL-6 and PDGF-A. J Clin Invest 1999; 103: 1253–1260.
9 Kawaguchi Y. IL-1a gene expression and protein production by fibroblasts from patients with systemic sclerosis. Clin Exp Immunol 1994; 97: 445–450.
10 Duan H, Fleming J, Pritchard DK et al. (2008) Combined analysis of monocyte and lymphocyte messenger RNA expression with serum protein profiles in patients with scleroderma. Arthritis Rheum 58:1465–74.
11 Maekawa T, Jinnin M, Ohtsuki M, Ihn H. Serum levels of interleukin-1α in patients with systemic sclerosis. J Dermatol. 2013 Feb;40(2):98-101. doi: 10.1111/1346-8138.12011. Epub 2012 Oct 18.
12 Kawaguchi Y,
13 Denton CP, Khanna D, Systemic sclerosis. Lancet 2017; 390: 1685-1699.
Source: XBiotech Inc.