Maarten Hulsmans, MS, PhD

Matthias Nahrendorf, MD, PhD

Fibrosis, or scarring, in the atria can disrupt the heart’s normal electrical signaling and drive atrial fibrillation (AFib). Therefore, identifying new ways to prevent or slow fibrosis has been a key focus for Mass General Brigham researchers such as Matthias Nahrendorf, MD, PhD, and Maarten Hulsmans, PhD, of the Center for Systems Biology. They are the senior authors of a recent study exploring the feasibility of a new precision therapy to safely interrupt the scarring process at the cellular level.

Their study aimed to selectively silence the Spp1 gene in a specialized subset of cardiac immune cells known as TREM2⁺ macrophages. In disease, these cells turn on Spp1 to produce osteopontin, a signaling protein that promotes inflammation and scarring in the heart. The researchers engineered an antibody–siRNA conjugate (ARC) that enabled the delivery of gene‑silencing treatment directly to these TREM2⁺ macrophages while largely avoiding other heart cells.

After testing the drug in multiple preclinical models, including mouse models of AFib and human heart tissue, they observed efficient silencing of Spp1 in the targeted immune cells, which in turn reduced pro‑fibrotic activity. After four weeks of ARC treatment, inducible AFib was significantly suppressed in mice without evidence of toxicity or other negative side effects, positioning this approach as a promising therapeutic avenue for curbing scarring in the heart.

Published in Nature Cardiovascular Research on April 23, 2026 | Read the paper: “Therapeutic Spp1 silencing in TREM2+ cardiac macrophages suppresses atrial fibrillation”

Summary reviewed by: Matthias Nahrendorf, MD, PhD; Maarten Hulsmans, MS, PhD