UPMC Newborn Medicine Program Expands Translational Research Studies of Novel Platelet Therapeutics
December 15, 2021
Platelets supplied by blood banks serve a critical need in the prevention and treatment of bleeding in neonates requiring major surgery or placement on extracorporeal membrane oxygenation (ECMO). Unfortunately, there are often shortages of this blood product as it only has a shelf life of 5 to 7 days before it must be discarded. Thus, many smaller communities and countries with limited medical services may not be able to provide this life saving blood product, especially to women with postpartum hemorrhage or babies with bleeding problems.
The Diacovo Laboratory at UPMC Children’s Hospital of Pittsburgh, led by Thomas G. Diacovo, MD, chief of the UPMC Newborn Medicine Program, has worked to upend this suboptimal treatment paradigm with new research and revelations, technological advances, and novel animal models that will lead to important new clinical trials in neonatal subjects.
Novel Platelet-Based Agent in Development by Cellphire Therapeutics
Cellphire Therapeutics is developing the next generation of platelet-based therapies that are long-term, shelf-stable, and could more rapidly treat bleeding. Until now, donated platelets had a shelf life of 5 to 7 days. However, the patented technology developed by Cellphire Therapeutics allows for freeze-drying platelets—stabilizing them—so they can last for years. If the forthcoming clinical studies of their investigational product called Thrombosomes® are successful and achieve U.S. Food and Drug Administration approval, the product could be given to patients anywhere at any time.
Diacovo Laboratory Leading Validation Studies of Thrombosomes®
The Diacovo Laboratory at UPMC Children's was sought out and is being funded by Cellphire Therapeutics to help validate their novel Thrombosomes® product using proprietary platelet function assays developed by Dr. Diacovo and colleagues that include a patented humanized mouse model that supports human but mouse-mediated hemostasis and thrombosis.
The model created by the Diacovo Laboratory is the only one of its kind in the world capable of directly assessing the function of new platelet products and drugs designed to inhibit the function of human platelets for preventing thrombosis.
In fact, this model was used to develop a new therapy to prevent thrombosis in neonates with congenital heart disease after undergoing surgical repair.
Future Clinical Trials of Thrombosomes® at UPMC Children’s
The initial work to validate the safety and efficacy of the novel Thromobosomes® product will include two clinical trials.
The first investigation will examine the use of Thrombosomes® as a therapy to correct bleeding due to antiplatelet therapies.
The second trial will study the use of Thrombosomes® to combat postpartum hemorrhage.
Prior Studies of Note by the Diacovo Laboratory
The investigational strength of the Diacovo Laboratory in studying antithrombotic agents in understudied patient populations, coupled with its technological prowess and novel assessment tools, were key to the lab being selected to conduct validations studies for the new Thrombosomes® agent.
High impact and novel recent findings from the Diacovo Laboratory include the following published studies:
• Chen JC, Tan K, Zhao H, Tronik-Le Roux D, Liddington RC, Diacovo TG. Modifying Murine von Willebrand Factor A1 Domain to Permit In Vivo Assessment of Human Platelet Therapies. Nat Biotech. 2008; 26: 114-119.
o News and Views of Nature Biotechnology editorial: “Humanizing mouse thrombi” Ingo Ahrens & Karlheinz Peter. 2008
• Magallon J, Chen JC, Rabbani L, Dangas G, Yang J, Bussel J, Diacovo T. Humanized Mouse Model of Thrombosis Is Predictive of the Clinical Efficacy of Antiplatelet Agents. Circulation. 2011; 123: 319-326.
This is the first publication to demonstrate a mouse with humanized VWF can be used in preclinical studies to test and predict the clinical efficacy of antiplatelet agents used in patients with cardiovascular disease.
• Kaza E, Egalka M, Zhou H, Chen J, Evans D, Pratts J, Li R, Diamond SL, Vincent J, Bacha E, Diacovo TG. P2Y12 Receptor Function and Response to Cangrelor in Neonates With Cyanotic Congenital Heart Disease. JACC Basic Transl Sci. 2017; 2(4): 465-476.
• Vargas D, Zhou H, Yu X, Diamond S, Yeh J, Allada V, Krishnamurthy G, Price M, Allen B, Alexander J, Schmidhofer J, Kreutzer J, Vincent J, Morell V, Bacha E, Diacovo T. Cangrelor PK / PD Analysis in Post-Operative Neonatal Cardiac Patients at Risk for Thrombosis. J Thromb Haemost. 2021 Jan; 19(1): 202-211.
Learn More About Dr. Diacovo, the Diacovo Laboratory, and the UPMC Newborn Medicine Program at UPMC Children’s Hospital of Pittsburgh and UPMC Magee-Womens Hospital.
