High CCL24 levels in SSc associated with more severe disease
Data reinforce development of antibody CM-101 for treating scleroderma
Blood levels of CCL24 are elevated in systemic sclerosis (SSc) patients compared to healthy people, according to a recent scientific presentation.
Consistent with previous studies, higher CCL24 levels correlated with SSc severity, a threefold greater risk of interstitial lung disease (ILD) progression, and shorter five-year survival rates.
“These results are consistent with the findings of our previous studies in SSc preclinical models and patient samples showing that higher CCL24 levels reflect more severe disease and can predict its prognosis,” Adi Mor, PhD, co-founder and chief scientific officer at Chemomab Therapeutics, and a study author, said in a press release.
Supported by these findings, Chemomab is developing its lead candidate CM-101, an anti-CCL24 antibody for treating SSc.
The data “reinforce the therapeutic rationale for the potential clinical utility of CM-101, our first-in-class anti-CCL24 antibody that aims to break the fibro-inflammatory vicious cycle we believe is central to the pathophysiology [development] of SSc,” Mor said.
Enrico De Lorenzis, at the U.K.’s Leeds Institute of Rheumatic and Musculoskeletal Diseases, presented the results in the poster, “CCL24 serum concentration predicts both vascular and fibrotic complications in systemic sclerosis,” at the 2023 European Congress of Rheumatology (EULAR) in Milan, Italy.
CCL24 blood levels and SSc disease severity
Blood CCL24 levels were compared between 181 SSc patients (13% males; median disease duration, four years) enrolled in a single-center, observational study, and age- and sex-matched healthy controls.
CCL24 is a chemokine, a protein that works as chemical attractant to immune cells. It “may be involved in both vascular and fibrotic manifestations of SSc,” the researchers said, based on the results.
CCL24 was deemed high when levels were above the upper quartile of controls, 110 nanograms/ml.
A total of 37 patients (27%) had diffuse cutaneous SSc and almost half (48%) had digital ulcers at the assessment or in the previous six months. Sixty patients (32%) had interstitial lung disease (ILD), a group of lung disorders marked by inflammation and scarring.
Elevated CCL24 levels were found in 52 patients (26%). This group had a significantly higher Rodnan Skin Score of skin thickness (median 4 vs. 2) and a higher prevalence of digital ulcers (60%). The prevalence of ILD was also higher (42% vs. 28%), though the difference was not statistically significant.
“These new data add to previous observations of elevated CCL24 levels in SSc patients and reinforce the therapeutic rationale supporting inhibition of CCL24 as a potentially effective treatment for SSc and other fibrotic [scarring] conditions,” De Lorenzis said.
In preclinical work with a mouse model of SSc, CM-101 safely and effectively blocked CCL24, reducing fibrosis. It also lowered the transition of fibroblasts to myofibroblasts, the cells responsible for the synthesis and buildup of scar tissue, in blood samples from patients.