Improved Mouse Models for the Study of Treatment Modalities using Sulfur-containing Small-molecular-Weight Molecules for Passive Immune-mediated Thrombocytopenia

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. To test the efficacy of novel sulfur compounds as alternative treatments for ITP, we used a mouse model of passive immune thrombocytopenia (PIT). Using this model, the platelet nadir could not be maintained, with platelet counts rising after day 4, despite daily anti-platelet antibody administration. We examined reticulated platelet counts by flow cytometry, and found increased thrombopoiesis in the bone marrow to be at least partially responsible for this platelet rebound. Consequentially, two improved mouse models of PIT were developed, where the platelet rebound is circumvented. The first model employs sublethal total body gamma-irradiation in combination with daily antibody administration, while the second model employs gradual escalation of the daily antibody dose. Finally, we show that none of the tested candidate compounds show efficacy in elevating platelet counts in vivo, likely due to their limited solubility.MAS