Although correcting the genetic abnormality remains the cornerstone of treatment for Duchenne muscular dystrophy (DMD), the fibrosis associated with the disease may limit its effectiveness.
A team of researchers, notably from France, injected CAR-T cells targeting FAP (Fibroblast Activation Protein) – a protein highly expressed by active fibroblasts – into mouse models of cardiac dystrophy (D2.mdx) following lymphodepletion.
- The CAR-T cells migrated to the target organs, notably the heart and skeletal muscles, where they reduced the expression of FAP and markers of fibrosis.
- These changes were correlated with a reduction in pathogenic FAP+ fibroblasts in these tissues.
- Cardiac function in the treated mice improved for up to five weeks after treatment; compared with control mice, the researchers noted, in particular, a significant improvement in left ventricular ejection fraction (LVEF).
This proof-of-concept study suggests that anti-FAP CAR-T cell therapy could be effective in mitigating fibrosis and cardiac dysfunction, and thus complement gene therapy.
