RAP-GRL

RAP-GRL is a recombinant fusion protein designed as a luspatercept-like transforming growth factor-beta (TGF-β) ligand trap. Developed by researchers at the Children's Hospital of Philadelphia and the University of Pennsylvania, RAP-GRL is modeled after the murine luspatercept analog RAP-536. It consists of the extracellular domain of human activin receptor type IIB (ACVR2B) fused to a mouse IgG2 Fc domain. RAP-GRL acts by binding and neutralizing specific TGF-β superfamily ligands, such as GDF11, GDF8 (myostatin), and activin B, thereby inhibiting aberrant SMAD2/3 signaling and promoting erythropoietin-independent maturation of late-stage erythroid cells. In preclinical models of β-thalassemia, RAP-GRL has been investigated both as a monotherapy and in combination with TMPRSS6 antisense oligonucleotides (T-ASO) to simultaneously improve ineffective erythropoiesis and iron overload.

Other names

activin receptor IIB ligand trap RAP-GRLluspatercept-like drugluspatercept-like proteinTGF-beta ligand trap RAP-GRL