Since 1964, the Lindsley F. Kimball Research Institute (LFKRI) has conducted groundbreaking research, resulting in numerous landmark patents and licenses as well as new blood-related products, techniques, and therapies. Today, they remain at the forefront of blood research by leveraging the resources of New York Blood Center Enterprises (NYBCe) to further our understanding of blood diseases and improve patient outcomes.
LFKRI currently consists of 20 pioneering investigators studying transfusion epidemiology, blood component therapeutics, transfusion-transmitted infectious disease, and transfusion immunology. One such investigator is Bruce Sachais, MD, PhD.
In addition to being an Associate Member of LFKRI, Dr. Sachais is also the Enterprise’s Chief Medical Officer and Head of the Platelet Research Laboratory. Currently, the Platelet Research Laboratory is focused on improved diagnosis and novel therapeutics for heparin induced thrombocytopenia (HIT). Dr. Sachais recently sat down with NYBCe representatives to discuss this research further.
Q: You’re currently involved in research on Heparin-Induced Thrombocytopenia (HIT), a rare adverse outcome of procedures that use heparin therapy, such as catheter usage and cardiac bypasses. In layman’s terms, can you briefly explain how the pathology of HIT occurs?
Dr. Sachais: Yes. Heparin is a drug that people may have heard of. It’s used to thin your blood, so that your blood doesn’t clot. Heparin-induced thrombocytopenia is a reaction to the heparin in combination with a molecule that’s naturally occurring in your platelets called platelet factor four or PF4.
Those two molecules (heparin and PF4) get together and cause antibodies to form. As a result, instead of thinning your blood, you then actually clot. Some people can have very significant clots, and it can even lead to death.
Q: And heparin is normally administered to prevent or stop clotting — so that sounds paradoxical. How does that happen?
Dr. Sachais: It does sound paradoxical and, most of the time, you’re right. When you get a thrombocytopenia or a drop in your platelets, you bleed — which is also a side effect of heparin — but here you clot. And that’s because there’s activation of the platelets as well as other cells in your blood vessels, such as any of endothelial cells and macrophages.
The activation of the cells leads to increased clotting potential. It can promote inflammation, but also it promotes clotting. So, the platelets are essentially being activated and used rather than just being cleared away, like in many thrombocytopenias.
Q: Specifically, what do you and your team hope to accomplish with your research on this subject?
Dr. Sachais: When I started this research, we didn’t know. We only knew a few things about how heparin-induced thrombocytopenia worked. Eventually, we figured out that for the heparin and the PF4 to get together and cause this disease, the PF4 had to form tetramers. And if you could do things to stop the PF4 from forming tetramers, you could stop the complexes as we knew them.
The hypothesis was: if we can stop the complexes from forming, we could affect downstream pathophysiology. In other words, prevent the drop in platelet count, prevent the clotting, and interfere with the whole mechanism of HIT.
Then, in collaboration with Fox Chase Chemical Diversity Center and Jefferson University, we developed a novel inhibitor of HIT that targets PF4 tetramerization. The goal of the drug is to stop the heparin-induced thrombocytopenia right at the source — where the heparin and PF4 interact with each other. This is the first type of treatment for HIT that’s really mechanism-based.
Currently, what we do is we just stop administering heparin. But these are patients that are on heparin for a reason — because they have some kind of clotting problem going on.
Non-heparin anticoagulants are then used in place of heparin. But the problem is, once the HIT has started, the other anticoagulants don’t work terribly well. And they also have bleeding risk. So, patients are put on these other drugs, and they have a bleeding risk and it doesn’t really protect them that much from HIT. We need something better.
Q: How long have you been conducting research on this drug in particular and HIT as a whole?
Dr. Sachais: I’ve been researching HIT itself for over a dozen years, and this specific molecule for the last several years.
Q: So, has this been your area of focus the entire time you’ve worked for LFKRI and NYBCe?
Dr. Sachais: I’ve been at the Enterprise for a little over six years. My undergraduate background was in chemistry, so even though I didn’t stay in chemistry, a lot of my projects are related to chemistry and the development of molecules and understanding how they work to help further research in other blood-related fields. But my HIT research and a pathogen inactivation project — I picked up those interests while with NYBCe.
Q: What kind of impact do you think this research will have for patients?
Dr. Sachais: The biggest impact it would have is to allow safer use of heparin — which is an important drug, even with new anticoagulants that are out there. There are advantages of heparin for many clinical situations. And in some cases, it’s really the only reasonable alternative for patients, especially patients who are undergoing bypass surgery, for example. Other anticoagulants don’t really do the job very well.
Q: What are your next steps for this project?
Dr. Sachais: We have actually identified a lead molecule that we think could move us toward our first in-human study, so the next big step is to raise money to help us reach what’s called an Investigational New Drug Application or IND. The IND contains all the data you need to provide the FDA to get them to agree that you can, in fact, safely administer a drug to humans.
We know some very basic things about the novel inhibitor’s safety, including potential side effects and lack of potential side effects and how it might be metabolized. But not nearly in enough detail. Everything looks good so far, but we need to do much more extensive studies that would go into the IND application for FDA review.
So really, the next big need for us — both scientifically and financially — are the same. And that’s to be able to do those IND-directed studies. To be able to write an IND and design an initial trial and then present all that to the FDA for evaluation.
Q: Out of curiosity, has the COVID-19 pandemic affected your research at all?
Dr. Sachais: It’s certainly slowed things down because we have to limit the amount of people who can be in the lab at one time. Luckily, though, everything is still progressing.
Q: How has working at NYBCe and LFKRI propelled your research — both with HIT and other areas — forward?
Dr. Sachais: The New York Blood Center offers a lot of opportunities since we’re not located in just one academic center. We have access to a lot of different disciplines. We have not only the scientific expertise but also the practical knowledge to pose a scientific question and then turn that into a real-world problem that we can solve. Plus, since we do have such a prominent place in the industry, it helps us attract partners who can further advance our research.
Dr. Sachais and NYBCe are actively seeking development and commercialization partners with the strategic focus and financial wherewithal to bring the PF4 antagonist through the global development, regulatory approval, and commercialization processes. Click here to Contact the Office of Ventures & Technology Development (VTD) and learn more about this opportunity.
There are other ways to support research like that of Dr. Sachais and other LFKRI investigators, too. Financial contributions go a long way to advance NYBCe’s groundbreaking research as well as help the non-profit continue their everyday life-saving operations during the COVID-19 pandemic. To make a gift online now, click here. You can also contact the Office of Philanthropy directly to learn more about the organization’s philanthropic needs.