Amphiregulin nanobodies to prevent the development of fibroatheromas

Researchers at Stanford have discovered that nanobodies blocking amphiregulin (AREG) activity have the potential to impede the progression of early-stage atherosclerotic plaque lesions to advanced-stage fibroatheromas.

Coronary artery disease is a chronic inflammatory disease characterized by the build-up of atherosclerotic plaques. In the early stages, the plaques are rich in lipids and can be treated with medication and lifestyle changes. However, as they mature beyond the lipid-rich phase, a subset of activated T-cells within the plaques expresses the pro-fibrotic protein AREG. This protein promotes smooth muscle cell proliferation and fibrosis, leading to advancement of lesions into irreversible advanced-stage plaques, such as fibroatheroma. Fibroatheroma is a major precursor to plaque rupture that could lead to life-threatening acute cardiac syndromes.

To prevent the development of fibroatheromas, Stanford researchers have devised a nanobody-based platform that blocks the attachment of AREG to atherosclerotic plaque lesions, hindering disease progression. The nanobody is a bispecific protein with two immunoglobulin single variable (ISV) domains: one ISV domain binds to AREG and the other domain interferes with vascular smooth muscle cells activity. This nanobody-based platform targeting the root cause of fibroatheroma development could revolutionize treatment strategies for patients with coronary artery disease.

Stage of Development
Proof of concept