In this Innovator Series article, AAKP interviews Joe Tector, MD, PhD, FACS, Founder of Makana Therapeutics
Founded in 2009, Makana Therapeutics is focused on developing pigs with reduced xenoantigen expression, making human transplantation of cells, tissues, and organs from these animals possible. Makana’s focus on simplified genetics, optimized pig production techniques, and careful patient selection
(including a proprietary crossmatch assay) is expected to streamline product development and result in safer, more efficacious products.
Tell us about your first experience with a kidney patient, personally or professionally, and what impressions that left on you as a fellow human being.
My first interaction was as a surgical resident seeing patients tethered to a dialysis chair in a dingy room for hours, and hours looking drained of all energy. This made me feel incredibly sad for these people who then had to go on with their day, trying to manage being a parent, an employee working to support their family, or simply to survive to the next dialysis treatment. It was a really heartbreaking scene.
Can you tell our AAKP national and global audiences why and how Makana first came into the kidney disease space and about the company’s commitment to kidney patients and their families?
Makana Therapeutics was spun out of my laboratory at Indiana University School of Medicine. Our entire professional existence was devoted to the development of an unlimited source of donor organs for individuals on transplant waiting lists. The use of pig kidneys could help reduce the shortage of donor kidneys. However, patients have antibodies that bind to key sugars on the cell surface of the pig cells that attack the pig kidney. We researched this key problem and came up with a solution. In 2014-2015, we were able to identify three genes in the pig that needed to be deleted in order to support pig to human capability; this genetic modification is currently known as the triple knockout pig. At that time, we also found that 30 percent of patients on the transplant waitlist do not have antibodies that attack this triple knockout pig, so we felt it was time to drive our work into human clinical trials.
As we know, there is a shortage of kidneys available for transplantation and hundreds of thousands of patients on dialysis and the transplant the waiting list. Can you share a bit about the science behind Makana’s research in xenotransplantation as a potential option to address this issue?
Makana has used two key approaches to make it possible to transplant a pig kidney into a human patient. First, we used gene scissors (CRISPR/Cas9) to edit the pig genome and remove specific sugars off the surface of the pig cell. This ensures that these new triple knockout pigs have kidneys that are compatible with at least 30 percent of patients on the current waitlist. These patients could receive this triple knockout pig kidney without risk of early rejection that has stopped xenotransplantation from moving to the clinic.
The second key to our approach is that we have developed the tissue typing tools necessary to identify which patients can actually benefit from receiving a triple knockout pig kidney. We have followed the developments in human tissue typing to bring the pig tissue typing up to speed. This allows us to give a patient with kidney failure the best chance to do well and resume a more normal life.
Pig to human xenotransplantation itself is not new to science. Since the 1960s, bioprosthetic heart valve (BHV) replacement has been occurring, however advancements have been made giving promise to potential clinical trials in pig to human solid organ transplants. Knowing there are a few companies in the xenotransplant space, can you share with us what makes Makana’s approach to xenotransplantation unique?
Makana is perhaps different than other efforts because it has been driven from the beginning by clinical surgeons who have brought all the core organ transplant competencies into our effort so that we are entirely comprehensive and have minimized the need for outsourcing to achieve our goals. The fact that Makana has comprehensive in-house capabilities allows us to drive our own data and interpretation of that data to be included into our effort without lengthy delays or debates so we can make xenotransplantation in the kidney space a safe and viable option for patients.
Innovation in the kidney space is important to patients to increase options and support care choice. Patients want to be involved in research opportunities and have their voice be heard. How do you suggest patients get involved in the concept of xenotransplantation, from understanding what it is to ensuring their unique insights and voices are heard?
It is important for patients to articulate how kidney diseases impact not only their health, but their life day to day and what they would be willing to do/accept to improve their situation. Also, it is really important for healthcare providers and policymakers to understand how much a patient is willing to risk versus what they expect to gain so we can be more balanced in what we propose for patients with kidney failure and avoid an approach where we assume we know what kidney patients want and their risk tolerance.
We understand that Makana recently received an important European patent that will catalyze xenotransplantation efforts abroad by making genetically modified pigs for use as organ donors for human recipients. What exactly does this mean and are there any projections for U.S. patients?
We are excited that the European patent office recognized that Makana developed a novel gene editing strategy for donor pigs that will be the backbone for any pig used as a pig kidney donor. The triple knockout pig was a major advancement for this field and provides patients with hope that there is innovation happening in transplantation and we may be able to soon say there is another transplant option. We are optimistic that the U.S. Patent Office will also recognize Makana with a patent for identifying this pig years before it was clear to anyone that these genetic modifications would help us overcome the antibody problem for xenotransplantation.
As a leader in healthcare, you know well that it is not easy to develop a novel approach to treat or enhance care. What do you draw upon internally to keep your drive, optimism, and focus on patients during the tough days?
The thought of so many people suffering while waiting for a transplant keeps us going even when it seems like all is lost. It is impossible to forget the wretchedness and suffering that accompanies kidney disease.
Final question–AAKP patients think this last question reveals a lot about a person–who is one of your heroes and why?
My personal heroes are people who pursue really important things for humanity for a very long time, long after most have abandoned the pursuit because of the hopelessness of the situation. Two heroes I would identify are 1) Winston Churchill, who inherited a seemingly impossible situation to stare down perhaps the greatest evil the world has ever known and bring peace to the human race and 2) Thomas Starzl, a transplant surgeon who worked tirelessly for more than 50 years to bring transplantation from a laboratory pursuit to a therapy that transformed the lives of hundreds of thousands of patients who otherwise had no hope and no possibility of a good life.
Dr. Tector has more than 30 years of experience in transplant surgery and as as director of the Xenotransplant Institute and surgical director of the Small Bowel and Multivisceral Transplant Program at the University of Miami Medical School. Dr. Tector received his training from McGill University, University of Miami, and St Louis University School of Medicine.