In our new preprint we explore whether genetics support targeting IL6 for cerebral small vessel disease

𝐍𝐞𝐰 𝐩𝐫𝐞𝐩𝐫𝐢𝐧𝐭 𝐢𝐬 𝐨𝐮𝐭: we explored with human genetic data 𝐈𝐋-6 𝐬𝐢𝐠𝐧𝐚𝐥𝐢𝐧𝐠 as a potential therapeutic target for 𝐜𝐞𝐫𝐞𝐛𝐫𝐚𝐥 𝐬𝐦𝐚𝐥𝐥 𝐯𝐞𝐬𝐬𝐞𝐥 𝐝𝐢𝐬𝐞𝐚𝐬𝐞 (𝐜𝐒𝐕𝐃) 🧠🧬—a major cause of stroke, dementia, and late-life disability.

Despite its public health burden, 𝐜𝐒𝐕𝐃 𝐬𝐭𝐢𝐥𝐥 𝐥𝐚𝐜𝐤𝐬 𝐝𝐢𝐬𝐞𝐚𝐬𝐞-𝐦𝐨𝐝𝐢𝐟𝐲𝐢𝐧𝐠 𝐭𝐫𝐞𝐚𝐭𝐦𝐞𝐧𝐭𝐬 ❗

With anti-inflammatory therapies (targeting IL-6 signaling) emerging for atherosclerosis, we asked:
👉 Could these therapies be repurposed for cSVD?
👉 Should cSVD-related stroke patients be included in trials of anti-inflammatory treatments (relevant in the emergence of such trials)?

We proxied IL-6 signaling downregulation with:
1️⃣ A genetic instrument of 26 CRP-lowering IL6R variants.
2️⃣ The well-characterized rs2228145 missense variant.

We evaluated:
👉Clinical outcomes (small vessel stroke, vascular dementia, etc.)
👉MRI traits (white matter hyperintensities, microbleeds, etc.)
👉Pathology (arteriolosclerosis in brain autopsy).

Findings:
❌ No evidence for any effects on cSVD-related outcomes.
✅ Significant associations with lower risk of large artery atherosclerotic stroke and carotid atherosclerosis (positive controls).

𝐁𝐨𝐭𝐭𝐨𝐦 𝐥𝐢𝐧𝐞: Genetic data do not support IL-6 targeting as a preventive therapy for cSVD.
 signaling for cerebral small vessel disease

Check out the preprint here: https://www.medrxiv.org/content/10.1101/2024.12.13.24318994v1

Great work with Larissa Tchuisseu Murad Omarov Joseph KAMTCHUM TATUENE ❗