Makana In The News
April 8, 2023
</p> <h4>National Public Radio Interview with Dr. Tector</h4> <p><a href="https://podcasts.apple.com/us/podcast/whats-health-got-to-do-with-it/id1585052184?i=1000608007008" target="_blank" rel="noopener"><img class="wp-image-224059 size-medium inthenewsImg" src="https://makanatherapeutics.com/wp-content/uploads/2023/04/whats-health-got-to-do-with-it-podcast-300x157.jpg" alt="What's health got to do with it - podcast" /></a> </p> <p><strong>What's Health Got To Do With It</strong><br /><a href="https://podcasts.apple.com/us/podcast/whats-health-got-to-do-with-it/id1585052184?i=1000608007008" target="_blank" rel="noopener">Listen to the Podcast now</a></p> <p>
March 9, 2023
</p> <h4>This Founder Is Getting Closer To Solving The Organ Shortage</h4> <p><img class="wp-image-224055 size-medium inthenewsImg" src="https://makanatheradev.wpengine.com/wp-content/uploads/2023/03/forbes-300x169.png" alt="Forbes" />Open</a>Today, March 9, is World Kidney Day, bringing greater awareness about the millions of people around the world with kidney disease, many of whom need transplants. Over 100,000 Americans are on waitlists for life saving organ transplants because of a chronic shortage of available organs. As often happens with limited supply, inequalities arise, and those from disadvantaged backgrounds, socioeconomic classes and—more often than not, women - are not able to access the transplants they need<a href="#toggle1" class="open-toggle1" id="open-toggle1">...read more.</a>
Surgeons are sometimes seen as the mechanics of the medical profession, so confident in their craft that there is no room to deviate from a well-trodden path. Dr. Tector has a surgeon’s telltale confidence. Unlike many surgeons, however, Dr. Tector’s tolerance for the unknown is a rare specimen in the medical field. To advance a vision like xenotransplantation means having the stamina to pursue an end goal that will be at least forty years in the making, if indeed it happens at all. I was inspired to chat with him how a surgeon’s frustration led him to dedicate his life to a solution that is redefining transplant care.
Dr. Tector, you are an experienced organ transplant surgeon. Tell me what led you to start a company focused on the pioneering research of xenotransplantation?
A transplant is enormously successful for patients, if they can get it. The reality is that the shortage of organs is a major barrier. Many people who need it don’t receive it. The technology of creating pigs as organ donors is a solution, and we started off by learning how to make those pigs. And then we learned that it wasn’t going to be feasible to get organs out of a university lab to those who need them, so we founded Makana Therapeutics.
As you’ve built this company and pursued xenotransplantation research at the Miami Transplant Institute. Talk to me about the hurdles you have had to overcome. What were the challenges you faced early on and how has that evolved as you’ve made progress?
As a surgeon, going through training, we are told to get a good mentor and follow a path. I was more project driven, I wanted to make xenotransplantation, this particular thing, happen. People would say that this is so far into the future, this is never going to happen. Then, the next obstacle was how we’d pay for it. Overall, the first barrier is to take down preconceived notions like these.
It was daunting for a surgeon. But, after making progress, it goes from nobody understanding what needs to happen to everyone understanding, and then people want to tell you what to do next. It can be very distracting, so you need to remain focused. A surgeon is focused on outcomes, so maybe that was my advantage. It’s a lot of work. And it never gets to the point where I say “this is easy, so now I can pick up some hobbies.” It takes a lot of persistence and focus.
We know that in organ transplants, waitlists are too long for everyone but women are waiting longer on average than men. Women are nearly 9 percent more likely to die when waiting for a kidneytransplant, 24 percent more likely while waiting for a liver transplant and 50 percent more likely when waiting for a lung transplant. Have you seen the human side of this gender disparity firsthand as a surgeon?
Those facts are real and upsetting. There are a couple of challenges that make it worse. Women are generally smaller than men. When a donor becomes available, if it is a large male, it can’t be transplanted to a small female. We don’t account for the time it takes for the next available organ for a specific individual when thinking about transplant lists. Xenotransplantation can eliminate this problem – because pigs come in all sizes.
Also, there is a very telling statistic on the scarcity from human donors today. On average, out of 1,000 deaths of people who have signed a donor card, only about 3 will have died in a manner that makes them suitable donors. We’ll never have enough organs from human donors even if everyone pledged to donate. Xenotransplantation is the logical solution.
I’ve read that pigs share 98% of genes with humans, which makes them potentially ideal animals for donating organs to humans. But have you seen resistance from a societal point of view to the notion of pigs being used in this way?
To the contrary, I’ve been impressed with how well people have received this. In the late 2000s, there was almost a frenzy around xenotransplantation. We have been coming along slowly on the scientific side, and people have seen the incremental steps. Surgeons have already been using submucosa pig tissue for meshes and heart valves with great success for years. It’s already a reality.
Explain to me in lay terms what the gene editing process is about and why it is such a big part of the research you have been doing.
It is driven by reducing pig organ rejection in the human body. If you look at cross-species transplantation, what has kept us from doing this successfully are antibodies in the host species that bind to cells from the transplanted organ. We are taking out the “gene scissors” and we are editing the pig’s DNA, so that the pig cells appear more similar to a human. One major advance in the past 10-12 years is the development of these so-called “gene scissors”. The creation of CRISPRS have allowed us to make gene edits in a very efficient manner. Our pigs have 3 genes knocked out, so there is a lot less antibody binding and this should mean greater success for the patient.
So, this gene editing process not only makes the organs more compatible but may help with some of the other concerns around communicable diseases. What else are you doing to ensure the health and wellness of future patients?
If there was a big concern, it is possible you can use gene editing to help with that. As it pertains to pigs and humans, pigs present a very low risk. Gene editing is in its infancy. As we introduce this into the clinic, there are many things that are considered. For regulatory concerns, the FDA (Food and Drug Administration) needs to get comfortable. You don’t want an organ that doesn’t have any immune capabilities. You need the organ to participate in the immune process.
As we’ve seen time and again with companies pushing boundaries in any field, regulators and lawmakers are often playing catch up. Have you been working with regulators like the FDA as you’ve been building and researching?
We have been working with the FDA. We presented our basic approach with the pig we intend to use, and what pathogen testing we are going to do to prevent any infections. They evaluated the barrier facility, immunosuppression we are going to do, and our preclinical data. They gave us one additional study to do before we can start a pilot trial.
That’s exciting to hear you are so close to clinical trials.
Yes, we are.
So, your passion is getting to the day where transplant surgeons can schedule a xenotransplant for a patient with kidney failure, or liver failure, or heart failure, well in advance, with adequate preparation and plenty of perfected organs ready to use. How far off is that day, in your best estimate?
As I said, we are very close to clinical implementation. This is 40 years in the making. I do think that the situation you described will happen in my lifetime. If you were to ask me: do you have any idea what your next pig is after this triple knock out? I’d say, yes. It is going to be a slow entry, but if we are methodical about the future, the progress will speed up rapidly.
How do you stay committed to your mission? What motivates you?
It has possessed my entire being. I am married and I have 5 kids. But this has been soul possessing. If you see what transplant can do for an individual and for families, it is transformative. My dad was my role model and gave me so much, but having been a surgeon has been a huge driver for me. There are parts of this journey that people would tell me about, bad things, that I just didn’t see. My inability to see those bad things allowed me to keep going. Ultimately, there is a scientific goal and a solution for patients here, and that’s been the focus.
Talk to me about being a surgeon and a founder. How did you manage? Both jobs are extremely demanding.
That has been an evolution, There were times when it was unbelievably hard to do both. But ultimately my clinical practice informed what we were doing which drove our key decisions. We have a fantastic CEO at Makana, Mark Platt. In the areas that I am helpful, he wants my input, and then I am cognizant that there are parts of the business that I shouldn’t be involved in. My team in Miami is incredible and they are supportive. They can clearly see how we are changing things for the better. That’s what you want in a team.
For more information on Dr. Joseph Tector’s xenotransplantation research at Makana Therapeutics, click here.
February 6, 2023
</p> <h4>Washington Needs to Champion Breakthroughs on Organ Transplants</h4> <p> <img class="wp-image-224055 size-medium inthenewsImg" src="https://makanatherapeutics.com/wp-content/uploads/2023/04/the-well-news.jpg" alt="The Well News" /> Thanks to better treatments for more diseases like cancer and heart disease, Americans are living longer and life after 60 is becoming more active and productive. The trend is expanding, because by 2030 about one in five Americans will be 65 and older. Longer life can mean later retirement and an extended period of contributing more to society than is needed from it, a moral and economic miracle in the making, thanks to science.<a href="#toggle2" class="open-toggle2" id="open-toggle2">...read more.</a>
The only cure for either condition is transplantation, and demand for kidney and liver transplants far outweighs others. But less than half of needy patients in the U.S. can find a human donor each year. We will never catch up with current methods, because even if every American signed an organ donor card, we still wouldn’t come close to meeting the demand.
Organ and tissue transplants from animal donors have been studied for more than a century, and heart valve transplants from pigs have been successfully performed for more than 30 years. But American scientists in this field, called xenotransplantation, are racing to make the next big leap just as longer lives are turning a brighter spotlight on this area of medical science in desperate need for a breakthrough.
Dr. Joseph Tector, a renowned Florida-based transplant surgeon who leads the transplantation research program at the Miami Transplant Institute, has spent decades on creating gene-editing technology that can breed pigs who can donate viable kidneys and livers that can be successfully transplanted into human patients. After many promising advances, his Makana Therapeutics team and partners at several universities are preparing for clinical trials that could be a game changer for generations to come.
The similarities between pig and human organs are what spurred research in the field of xenotransplantation. Tector’s decades-worth of research has been aimed at breeding genetically altered pigs without key antigen blockers that play a role in organ rejection. This would dramatically lower the immune response to those organs in human recipients and increase the success rate for kidney and liver patients. His lab has already bred genetically advanced versions of these pigs for highly promising studies in primates as a last step before clinical human trials.
Today, the majority of Americans waiting for kidney and liver transplants are over the age of 50, with a sharply rising statistic among those 65 and older. These numbers point not only to higher demand in the future but growing need for so-called re-transplants, where donated organs reach the end of their effectiveness and a new transplant is needed to preserve the continued health of a patient.
This is especially true for kidney transplant recipients. Currently, donated kidneys last on average from 14 to 28 years before failing and requiring a new transplant. With Americans living longer, demand for kidneys will therefore multiply. This makes the need to solve the supply problem all the more urgent.
The worst thing that could happen to this rapidly advancing field of research is for the usual gears of Washington bureaucracy to grind it unnecessarily to a halt. The COVID vaccine effort was a hallmark in American achievement through Operation Warp Speed, but it took decisive commitment from both our political leaders and the best minds at the U.S. Food and Drug Administration to make it happen.
A similar meeting of the minds is needed to solve the organ shortage, now that Tector’s team has a possible solution in the works. Those of us in the trenches on health care advocacy must be vigilant again with an FDA that has a spotty record on innovation. We’ve come so far that we’ve revolutionized life after 60. Now is not the time to leave behind millions of Americans on transplant waitlists today and in the future who deserve to share in it.
</p> <h4>There Should Be An Urgency To Increase The Number Of Kidneys Available For Transplant</h4> <p> <img class="wp-image-224055 size-medium inthenewsImg" src="https://makanatheradev.wpengine.com/wp-content/uploads/2023/03/forbes-300x169.png" alt="Forbes" /> The United States has a government agency solely devoted to reducing automobile deaths in the United States, and it spends billions of dollars each year—and requires auto companies to do likewise—in an attempt to make our nation’s roads and the cars that travel on them safer. More people die from kidney disease than from automobile accidents, but we lack any concerted effort to reduce these deaths. <a href="#toggle3" class="open-toggle3" id="open-toggle3">...read more.</a>
We do spend a lot of money to care for people with end-stage renal disease: Over half a million people are currently on dialysis, and the federal government alone spends over $100 billion a year providing the treatment to people on Medicare, but living on dialysis is debilitating and it makes working and most other daily activities difficult.
Right now the only cure for someone with end-stage renal disease is a kidney transplant, but we have an enormous shortage of kidneys available for transplant: almost 25,000 Americans received a kidney transplant in 2021, but we need two to three times as many kidneys to alleviate the shortage.
There are three distinct efforts at the moment with the goal of increasing the amount of organs available. The first is to improve the performance and accountability of the 56 Organ Procurement Organizations—each assigned a fixed region of the country—that are tasked with procuring kidneys from willing donors—deceased or living—and getting them to those most in need of one.
Right now their performance varies widely: In some markets the rate of kidneys procured per decedent is two or three times that of other OPOs, with no apparent reason for the disparity. It is not uncommon for organs to be lost in transit, and the software to keep track of organs is antiquated or nonexistent.
The second way to boost the availability of kidneys would be to compensate live donors for the costs they incur in the process. The National Organ and Transplant Act prohibits paying people to donate, but the government can compensate them for the costs they incur traveling to and from the hospital as well as lost wages, childcare, or health costs not covered by insurance. One study estimated these costs average $38,000, and alleviating them would induce more people to make such a life-saving gift. The Trump Administration did issue an executive order to provide more funds to cover such costs, but the final regulation excluded anyone with an income over 350 percent of the poverty line from receiving any reimbursement, which greatly limited its efficacy, and the amount of compensation for those who are eligible is a fraction of the average costs incurred.
However, even radical improvements in OPO performance and cost reimbursement reform won’t get us there.
Fortunately, scientists have begun making considerable progress in the use of xenotransplantation by creating kidneys suitable for human transplant in pigs, which holds the promise of a permanent fix to our kidney shortage.
Xenotransplantation science uses gene-edited pigs that are bred to allow for their kidneys or livers to be conducive for human transplants. If successful, this could make an abundant supply of organs for transplant available in the next decade or two.
Eliminating the shortages of available organs is not the only benefit of xenotransplantation science. Gene editing is being used to modify the donor animals to eliminate antigen blockers, which can dramatically lower the immune response in people, potentially allowing transplant recipients to forgo taking autoimmune drugs. Such an outcome would dramatically improve the health outcomes and reduce the long-term cost of care.
U.S.-based Makana Therapeutics recently obtained a European patent for its pig that employs this gene editing innovation. Transplant surgeon Joe Tector, founder of Makana Therapeutics, is in talks with the U.S. FDA to launch first-even human clinical trials through the Miami Transplant Institute.
While this could potentially solve our shortage, FDA approval is at least a decade away—too late to help any of those currently afflicted with end stage renal failure
Over 100,000 people are currently on a transplant waiting list, and hundreds of thousands of others who could potentially benefit from a transplant do not go on the waiting list because there is no hope of them ever receiving one. Figuring out a way to solve the kidney shortage should be a matter of great urgency, but after spending a decade working on this issue I can tell you that few within the government appear to feel that way about it.
Solving this shortage would not only save tens of thousands of lives each year but it would also save the government tens of billions of dollars. It behooves us to hasten a solution to this terrible problem by supporting all efforts to obtain more kidneys.
</p> <h3>Hope is Just Around the Corner for Those Awaiting an Organ Transplant </h3> <p><img class="wp-image-224055 size-medium inthenewsImg" src="https://makanatherapeutics.com/wp-content/uploads/2023/04/dcjournal.jpg" alt="Forbes" /> For many people, a new year represents an opportunity for a fresh start. But for over 100,000 Americans waiting for an organ transplant, it means another year of anxiety and clinging to hope. A small portion of those patients will eventually get a transplant, though their health may deteriorate while they wait. But with each passing year, most people on the waiting list will not receive the life-saving organ they need. <a href="#toggle4" class="open-toggle4" id="open-toggle4">...read more.</a>
In the past decade, scientists have been diligently working to find innovative solutions to meet the shortfall and save lives. One of the most promising solutions: Pigs. At first glance, that animal may seem an unlikely candidate. In fact, pigs are a great candidate for organ supply because they are an extremely close physiological match for humans. Pigs have long been used successfully in medicine – including for skin grafts and heart valve transplants.
Now, cutting-edge scientists and transplant surgeons are charting the course for transplanting full pig organs into people who need a healthy organ. They believe that xenotransplantation, the process of transplanting organs or tissues from one species to another, holds the key to ending the organ shortage crisis.
In addition to providing an increased supply of organs, xenotransplantation from pigs can potentially improve the organ transplant success rate for patients. Many organ transplants fail due to rejection, in which the body’s immune system attacks and destroys the transplanted organ. Xenotransplantation can potentially reduce the risk of rejection by using organs that have been genetically tailored to reduce the immune response.
For example, Dr. Joseph Tector, a transplant surgeon at the Miami Transplant Institute and a leader in the field of xenotransplantation research, has crafted a new process for gene editing that his laboratory Makana Therapeutics calls the “triple knockout.” This unique and innovative technology removes three specific antigens that trigger the rejection of new organs. Innovations like this are what drive the science of xenotransplantation forward and closer to the day when no patient has to wait four or more years for a new organ.
This innovation may sound more like the plot of a futuristic movie than modern science, but the fact is that transplant surgeons and scientists believe clinical trials could be approved by the U.S. Food and Drug Administration (FDA) as soon as this year. As it considers that approval, it must consider the massive impact this science could have in saving patients’ lives. The federal government should be in the business of nurturing potentially lifesaving innovations with strict adherence to the best science. That’s why it is vitally important that the federal government, and specifically the FDA, balance patient safety with the urgent need for breakthroughs in the organ transplant space.
The recent pig heart transplant to a Maryland man last year, which may have failed due to viral contamination, showed both the promise of xenotransplantation and the urgent need for the FDA to set one, scientifically-focused standard for all its authorizations. It must ensure strict pathogen rules and high standards around pig donors are always met. That rule requires the FDA to be the gold standard for authorizations, while it prioritizes working with transplant innovators committed to that standard in science.
This emerging field of science and the hope that it can bring is closer to reality than many of us could ever imagine. When the day comes that xenotransplantation is the new standard for transplant surgery, it will be a lifesaving turning point for thousands of Americans on waiting list.
January 9, 2023
</p> <h3>Organs on demand: 10 Breakthrough Technologies 2023</h3> <p><img class="wp-image-224055 size-medium inthenewsImg" src="https://makanatherapeutics.com/wp-content/uploads/2023/04/mit-technology-review.jpg" alt="MIT Technology Review" /> </p> <p><strong>Engineered organs could put an end to transplant waiting lists.</strong><br /><strong>WHO</strong> - eGenesis, Makana Therapeutics, United Therapeutics<br /><strong>WHEN</strong> - 10 to 15 years</p> <p>For two months last year, a 57-year-old man named David Bennett lived with a pig heart beating inside his chest. Surgeons at the University of Maryland had put it there to see: Could a gene-edited pig’s heart keep a person alive?<a href="#toggle5" class="open-toggle5" id="open-toggle5">...read more.</a></p> <p>
Far more people need an organ transplant to live than can get one. There are around 130,000 organ transplants each year around the world, but many more people die waiting for an organ or because they never even made it onto a transplant waiting list.
Animal organs are one potential solution. But it’s not easy to overcome the human body’s natural revolt against them. For example, sugars on the surface of pig tissue can send our immune system into attack mode. Drugs can help mute the response, but it’s not enough. So biotech companies have used gene editing to modify pigs, removing those sugar molecules and adding other genes to make the pigs seem more human-like.
By editing the DNA of pigs in this way, several biotech companies have now created animals whose organs are more compatible with human bodies. Though Bennett died, and a virus was found in the transplanted organ, his doctors claim the pig heart he received never developed classic signs of organ rejection. Now they’re planning studies with more patients.
In the future, organ engineering might not involve animals at all. Researchers are in the early stages of exploring how to engineer complex tissue from the ground up. Some are 3D-printing scaffolds in the shape of lungs. Others are cultivating blob-like “organoids” from stem cells to imitate specific organs. In the long term, researchers hope to grow custom organs in factories.
Whether they’re grown in animals or built inside manufacturing plants, an unlimited supply of organs could make transplantation more common, and give far more people access to replacement parts.