Luspatercept (mIgG2a)

Hbb^th1/th1 mice of the B6.D2-Hbb^d3th/BrkJ strain (3-4 months old) with hydrogen peroxidenot (50 μM) or not^[1].

1 mg/kg

s.c., twice weekly for 2 months and then collected bone marrow, spleen and liver tissues.

Significantly increased 29% RBC number, 16% hemoglobin concentration, and 19% hematocrit.
Decreased 8% mean cell volume, 10% mean cell hemoglobin, and 2% mean cell hemoglobin concentration.
Reduced 33% reticulocytes and a 19% red cell distribution width area.
Induced an overall increase in the proportion of late-stage erythroid precursors, significantly decreased the cell population of R1 while an increase of R3 in bone marrow, and reduced R1 and R2 with a significant increase in R3 in the spleen.
Reduced ∼60% serum EPO level, 36% splenomegaly, serum concentrations of ferritin (15%) and iron (28%), 29% transferrin saturation.
Reduced iron levels in liver (1464 μg/mg dry weight) and kidney (648 μg/mg dry weight) and altered the iron distribution with restoration of architecture in spleen.
Increased Hamp mRNA levels approximately 2 times without the expression changes of Bmp6 in liver and Gdf15 or Twsg1 in spleen.
Reduced 40% mean concentrations of total bilirubin and occurrence of abnormal erythrocyte morphology and hemolytic debris, but increased mean erythrocyte life span (28 vs 20 days).
Markedly reduced heinz bodies and 38% mean membrane-associated α-globin aggregates in peripheral erythrocytes.
Reduced ROS levels significantly in immature (CD71+Ter119+) and mature (CD71−Ter119+) erythroblasts as well as in peripheral red cells.
Reduced peroxide-stimulated ROS levels and significantly increased 17% bone mineral density, 100% trabecular bone volume (100%), number (14%), and thickness (14%).
Increased cortical thickness with a decrease in marrow space.

Hbb^th1/th1 mice of the B6.D2-Hbb^d3th/BrkJ strain (3-4 months old)^[1].

30 mg/kg

i.p., once for 12 h, and then collected bone marrow, spleen and liver tissues.

Reduced phosphorylated Smad2/3 level in erythroid precursors of spleens within 12 h.
Inhibited phospho-Smad2 protein expression in erythroid precursors of spleens within 12 h.

C57BL/6 wild-type mice were injected intraperitoneally with EPO (1500 units/kg) or not^[1].

1, 10 mg/kg

s.c., (1 mg/kg) twice weekly for 2 months, (10 mg/kg) once for 72 h, and then collected bone marrow, spleen and liver tissues.

Promoted terminal erythroid differentiation in the bone marrow and spleen and increased peripheral red cells in EPO-pretreated wild-type mice at 10 mg/kg with EPO stimulation in C57BL/6 wild-type mice.
Did not affect iron parameters and Hamp expression in C57BL/6 wild-type mice.