Treatment with the novel small-molecule phagocytosis inhibitor Kotra-Branch (KB)-208 demonstrated effectiveness for improving thrombocytopenia, including fetal and neonatal alloimmune thrombocytopenia (FNAIT), which was similar to that with intravenous immunoglobulin (IVIG), according to a study was performed in a passive antibody mouse model of immune thrombocytopenia (ITP) published recently in the journal Transfusion.
Immune cytopenias are known as a group of autoimmune and alloimmune disorders that include FNAIT, hemolytic disease of the fetus and newborn, and ITP. The use of mouse models is common for studying the underlying mechanisms of action and possible treatment approaches for use in human immune cytopenias.
In patients with ITP, the process of extravascular phagocytosis takes place. In extravascular phagocytosis, macrophages (a type of white blood cell) in the liver and/or spleen are involved in the destruction of blood cells that have been “opsonized” by either autoantibodies or alloantibodies. Opsonization is described as a process that assists the immune system in the identification and elimination of old cells or pathogens. In fact, antibodies and immunoglobulins are common opsonins.
Recognizing that new therapies aimed at preventing phagocytosis should prove beneficial in patients with FNAIT and other immune cytopenias, the researchers sought to explore related therapeutic options in mouse models designed to simulate human immune cytopenias. Armed with the knowledge that KB-208 has previously demonstrated effectiveness for in vitro phagocytosis, they synthesized the agent via utilization of a passive antibody mouse model of ITP.
Read more about FNAIT testing and diagnosis
Following treatment of the mice with KB-208 for 60 consecutive days, toxicity was evaluated with use of a biochemistry panel, histopathology and gross necropsy.
Results of the study showed that KB-208 exhibited similar efficacy to IVIG for improving thrombocytopenia in all three mouse strains evaluated. The small-molecule agent was effective at a dose of 1 mg/kg for improving ITP, compared with an IVIG dose of between 1000 and 2500 mg/kg.
Of note, treatment with KB-208 had no effect on other blood parameters. Further, KB-208 treatment was not associated with elevations in serum markers of toxicity, and no abnormal histopathologic findings were reported.
“KB-208 is similar to IVIG for the amelioration of ITP in multiple mouse strains,” the authors highlighted. “These findings indicate that KB-208 is efficacious, without significant in vivo toxicities in mice, and is a potential small[-]molecule candidate for further evaluation to be used in the treatment of ITP and possibly all immune cytopenias [in which] phagocytosis is responsible for the pathophysiology,” they concluded.
