PBI’s active clinical research focuses on deep vein thrombosis, stroke, thrombophilia, thrombocytopenia, haemophilia A, recurrent miscarriage, Von Willebrand disease, leukaemia, lymphoma, myeloma, anaemia and iron overload. PBI’s research division, together with PBI’s clinical trials division, conducted early- and late-phase international clinical trials with new therapeutics developed through PBI’s clinical research.
The trials produced research publications in leading medical journals, including the Journal of Thrombosis and Haemostasis and the New England Journal of Medicine; and provided the basis for early access to new-targeted drugs for Australian patients.
An area of PBI's research is on the modification of next generation precision nucleic acid-based medicines (in collaboration with Dr Rakish Veedu), for the purpose of the treatment of blood diseases and other cancers. PBI’s research team was the first to understand the complex microRNA (miR) control of blood coagulation factors which led to the discovery of the proposed miR mechanism of oestrogen mediated thrombosis.
This research has resulted in new miR-based related blood diagnostic tests and miR-based therapies currently being developed.
Thrombotic Thrombocytopaenic Purpura (TTP) is a rare and fatal disease caused by a deficiency of the Von Willebrand factor cleaving enzyme, ADAMTS-13. ADAMTS-13 deficiency can be hereditary, but more often is an acquired disorder due to the production of inhibitory autoantibodies. It occurs in around 20 patients per year per million people. The PBI research division leads the Asia Pacific Microangiopathy Thrombocytopaenia (APMAT) Network across 24 leading centres in the Asia Pacific (AP) to rapidly collect and bio-bank clinical material on a large number of patients with Thrombotic Microangiopathy. Our work has standardised diagnostic ADAMTS-13 testing in the AP region, and utilising the APMAT bio-bank we are exploring new diagnostic algorithms and developing new molecular testing.
Our understanding of the rare TTP disease has led to a proposal for further research on the disease and a global standardisation study of ADAMTS13 testing.
Bleeding is a common complication of advanced chronic lymphocytic leukaemia (CLL). PBI’s research discovered important cancer-related platelet dysfunctions, which could contribute to the exacerbated bleeding phenotype seen in CLL patients. This could be particularly significant in malignant CLL clone and/or therapeutic interventions, where further impaired platelet function could be at play. One study examined Bruton’s tyrosine kinase inhibitors (eg. ibrutinib, acalabrutinib) and their effect on blood samples collected from patients. These drugs are known to inhibit platelet aggregation mediated by glycoprotein VI (GPVI) and other platelet signalling pathways. Furthermore, the study examined the anti-platelet effects of BH3 mimetics (eg. venetoclax), a less well understood property of the drug. CLL is associated with a broad platelet functional defect, which persists despite the clinical benefits of ibrutinib or venetoclax treatment.
Results of the study showed that ibrutinib, not venetoclax, induces additive inhibition of platelet function in CLL patients, that is not related to altered GPVI cleavage. Additionally, it was shown that clinically-utilised whole blood platelet function assays are capable of quantifying the degree of functional impairment in CLL patients - a world first observation made by PBI scientists.