Leonard Zon, M.D., the Grousbeck Professor of Pediatric Medicine at Harvard Medical School and the Director of the Stem Cell Program at Children’s Hospital Boston, is steeped in the science of stem cells. His research is centered on stem cell biology and cancer genetics, and he is credited with helping to develop induced pluripotent stem cells, cells from blood or skin that can be transformed into other tissues and organs.
More recently, the work of his company, Scholar Rock, has led to apitegromab, an antibody that can prevent muscle loss in those taking GLP-1 drugs. The antibody can also help children with spinal muscular atrophy, an inherited genetic disease that leads to progressive muscle weakness, who have shown improvement in walking from the antibody.
Another area of focus for Zon and his team involve mutations in blood stem cells, found in 13 percent of all 70 year olds, he said at DOC 2025 during his session, “Aging, Stem Cells, and Rejuvenation.” These cells pump out white blood cells, which “put out inflammatory cytokines,” and can lead to increases in strokes and heart attacks. The mutant stem cells can even show up in the stem cells of tumors. However, specific white blood cell macrophages — immune cells that consume bacteria, dead cells and other pathogens — can be employed to locate these stem cells and remove them.
“We can teach the white blood cells to eat the mutant clones of stem cells and then help in the aging and longevity process,” he said.
You can hear more from Dr. Zon in the video or read our lightly edited transcript below.
TRANSCRIPT
Dr. Leonard Zon
Thank you. Super great to be here, Jordan. It’s an amazing conference. Meet incredible people. I’m going to pick up where Helen, left off and, I talked about this a little bit last year. There’s a growth factor in your body called myostatin. And myostatin is a negative regulator of muscle. So if you look at these animals and the human on the left, they are mutated in myostatin. The cow there that you see is often called the Schwarzenegger cow because it is bulked up unbelievably. Those are carrying mutations. But my company, Scholar Rock, actually made an antibody, called apitegromab And this is, binding to myostatin and inhibits inhibits its activity. This, has been tested in a number of humans and it’s been quite remarkable.
The first is, there are children who have spinal muscular atrophy. This is a devastating disease. Many of these kids cannot walk or do anything. And, we, gave them our drug and, and improvement scale. They went up 1.8, points, but 30% of those patients, developed significant strength greater than three points. We had children who couldn’t walk. Then with our drug, they could walk. I have to say, for me, as a physician scientist, that was one of the most amazing thing. Actually meeting the patients, afterwards, it’s quite amazing. Now, since last year, we actually, did a trial, giving turns up beside the Lilly drug for weight loss.
As Helen highlighted, there’s a tremendous loss of muscle. Many of you who are on, the Lilly drug or, or in the Novo drug, have protein shakes and take a lot of things to try to keep up the proteins for the muscle. Well, if we give, at plus tears episode, you prevent the loss of muscle, from, the GLP agonist.
Now, if you think about all the uses that this drug could actually have, and, and, the safety was incredible. There was really very little problems with it. I think this could end up being a longevity drug and, you know, taking GLP using your natural body’s systems to weight loss and then adding in an anti-myostatin antibody to prevent the muscle loss makes a lot of sense.
These are some things over the next year that might come to bear. Now we’re all here to talk about longevity and aging. If you were to ask me what what is aging? Ten years ago, I would say it’s epigenetic. Epigenetic means you don’t know what the cause of it is. Okay. But a few friends of mine actually sequence the blood of old people. The surprise was there were mutations in blood stem cells in old people. There were particularly three genes that were mutated. All three of these gene genes are epigenetic regulators. This is incredibly common. If you see on the graph there, 13% of all 70 year olds have mutated stem cells. This is associated with, inflammation.
The mutant stem cells make mutant white blood cells that pump out inflammatory cytokines. The same ones that you were seeing, were activated by stress. But these are genetically programed to be very stressful. You end up getting strokes, heart attacks. Even if you have a stage one lung cancer and you have clonal hematopoiesis, you end up getting more tumors as a result. They even found mutated clones of stem cells in the tumors. We think that this is a large part of aging and a large part of heart attacks in the, in the world. We’ve started a chip clinic at Dana-Farber, clonal hematopoiesis of indeterminate potential. We have were overrun, overrun with patients, young patients who have heart attacks, who end up having heart attacks because they have mutant stem cells.
What I’ve been trying to do is to look at how to get rid of the mutant stem cells. What we found is that, a particular white blood cell macrophages, actually, kill stem cells. More often the macrophage comes in and it takes a bite of a stem cell. Then, once it takes the bite and removes a little material, 45 minutes later, the stem cell will actually divide. There’s this code of, quality assurance of your stem cells by these white blood cells. We’ve been able to actually, crack the code.What happens is, on the bottom, if you have a high oxidant stress in your stem cells, those stem cells are going to be doomed.
On the top, you see that this grooming behavior is driven by a don’t eat me signal. We think now using this code, we can teach the white blood cells to eat the mutant clones of stem cells and then help in the aging and longevity process. This is something that I’m taking to a new company, called Camino.
Lastly, I just want to finish with what most of the questions I’ve gotten in this meeting is about is, a lot of people are getting stem cell therapy. Jordan and I have a little clinic on stem cells, and, watching people have some results, but also watching people have a lot of toxicity. You might, have gotten mesenchymal stem cells. This is very common. Then more frequently, over the past 6 to 8 months, exosomes. So first of all, if you’re going to get these therapies, you might want to talk to Jordan or maybe, we’ve had a number of disasters happen. My message is you should know if you’re going to get stem cell therapy, what the stem cells are that are being put into your body. Some of these are offshore stem cells. They’re infected. It’s bad. We really need to watch out here. Now with exosome terms the literature is really not that great for this. About a lot of people take them and they contain all the things on this slide. Nucleic acids proteins and lipids. And we’ve recently found that stem cells actually secrete exosomes, blood stem cells in particular.
These macrophages that the white blood cells I was talking about get activated by these exosomes. Now for the first time, we’re studying these academically and seeing what’s in the exosomes, how do they, perturb the immune system. Maybe we’ll get to an answer. But again, if you’re thinking about exosome therapy, please talk to Jordan or me. We’re very happy to help you. That was my message for today and happy to take questions. Thank you. Okay.