Principal Investigator: Robert Goggs

Co-PI: Erica Behling-Kelly

DESCRIPTION (provided by applicant): 

Immune-mediated hemolytic anemia (IMHA) is the most common immune-mediated disease of dogs and is associated with a high mortality rate. The most clinically severe form of IMHA occurs when antibodies bound to erythrocytes fix complement causing intravascular hemolysis. Currently used therapeutics do not directly target this complement-mediated hemolysis, but rather globally suppress the immune system causing debilitating side-effects. We are collaborating with Aurin Biotech (http://aurinbiotech.com/), a pharmaceutical company that is developing a novel complement inhibitor (DAS) for human Alzheimer’s disease, to investigate its suitability as a drug for canine IMHA. Preliminary data demonstrate that DAS is a safe and highly effective inhibitor of canine complement-mediated hemolysis and as such could transform how we manage canine IMHA. We propose measuring the pharmacokinetics, pharmacodynamics and safety of DAS in mixed-breed dogs to enable a prospective, randomized clinical trial of this drug in dogs with IMHA. Specifically, we will assess pharmacokinetic parameters by repeated sampling of dogs following a single IV injection of DAS followed by measurement of plasma drug concentrations by mass spectrometry. Pharmacodynamics will be assessed by using ex vivo complement-mediated hemolysis inhibition assays. Drug safety will be confirmed through hematologic, biochemical and coagulation testing and by measurement of acute phase proteins and cytokines.