Kinase Inhibitors Effective Against GVHD

A recent study of various drug combinations that might reduce or eliminate graft-versus-host disease (GVHD) has shown that kinase inhibitors can lessen the severity of GVHD, which often develops after bone marrow transplantation.

Investigators at Parker Hughes Cancer Center (Roseville, MN, USA) used a mouse model where C57BL/6 mice received bone marrow grafts from allogeneic BALB/c donors. The mice were then treated with Parker Hughes' proprietary BTK (Bruton's tyrosine kinase) inhibitor, alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13), alone or in combination with the standard anti-GVHD drug methotrexate (MTX) or the novel anti-GVHD drug JANEX-1 (targeting Janus kinase 3).

Results published in the September 2004 issue of the British Journal of Hematology showed that untreated control mice developed severe GVHD and died an average of 40 days after the transplant. Mice treated with LFM-A-13 survived significantly longer, dying after an average of 47 days. The combination of LFM-A-13 and MTX was more effective, while mice treated with LFM-A-13 and JANEX-1 remained alive throughout the 80-day observation period.

The authors concluded that, "These results indicate that targeting BTK with the chemical inhibitor LFM-A13 may attenuate the severity of GVHD, especially when it is combined with other anti-GVHD drugs, such as MTX and JANEX-1.”




Related Links:
Parker Hughes Cancer Center