OK, let’s just take a second and recap. I’ve showed you that we can take our stem cells and differentiate them into cardiac muscle. We’ve learned how to keep them alive after transplantation, we’ve showed that they beat in synchrony with the rest of the heart, and we’ve shown that we can scale them up into an animal that is the best possible predictor of a human’s response.
You’d think that we hit all the roadblocks that lay in our path, right? Turns out, not.
These macaque studies also taught us that our human heart muscle cells created a period of electrical instability. They caused ventricular arrhythmias, or irregular heartbeats, for several weeks after we transplanted them. This was quite unexpected, because we hadn’t seen this in smaller animals.
We’ve studied it extensively, and it turns out that it results from the fact that our cellular graphs are quite immature, and immature heart muscle cells all act like pacemakers. So what happens is, we put them into the heart, and there starts to be a competition with the heart’s natural pacemaker over who gets to call the shots.
It would be sort of like if you brought a whole gaggle of teenagers into your orderly household all at once, and they don’t want to follow the rules and the rhythms of the way you run things, and it takes a while to rein everybody in and get people working in a coordinated fashion.
So our plans at the moment are to make the cells go through this troubled adolescence period while they’re still in the dish, and then we’ll transplant them in in the post-adolescent phase, where they should be much more orderly and be ready to listen to their marching orders. In the meantime, it turns out we can actually do quite well by treating with anti-arrhythmia drugs as well.
So one big question still remains, and that is, of course, the whole purpose that we set out to do this: Can we actually restore function to the injured heart?
To answer this question, we went to something that’s called “left ventricular ejection fraction.” Ejection fraction is simply the amount of blood that is squeezed out of the chamber of the heart with each beat. Now, in healthy macaques, like in healthy people, ejection fractions are about 65%. After a heart attack, ejection fraction drops down to about 40%, so these animals are well on their way to heart failure.
In the animals that receive a placebo injection, when we scan them a month later, we see that ejection fraction is unchanged, because the heart, of course, doesn’t spontaneously recover.
But in every one of the animals that received a graft of human cardiac muscle cells, we see a substantial improvement in cardiac function. This averaged eight points, so from 40% to 48%.
Now you might say 8 points. Is that big deals or little deal, what does 8 points actually mean in this context?
What I can tell you is that 8 points is better than anything that’s on the market right now for treating patients with heart attacks. It’s better than everything we have put together. So if we could do eight points in the clinic, I think this would be a big deal that would make a large impact on human health.
But it gets more exciting. That was just four weeks after transplantation. If we extend these studies out to three months, we get a full 22-point gain in ejection fraction.
Function in these treated hearts is so good that if we didn’t know up front that these animals had had a heart attack, we would never be able to tell from their functional studies.
Going forward, our plan is to start phase one, first in human trials here at the University of Washington in 2020 — two short years from now. Presuming these studies are safe and effective, which I think they’re going to be, our plan is to scale this up and ship these cells all around the world for the treatment of patients with heart disease. Given the global burden of this illness, I could easily imagine this treating a million or more patients a year.
Our vision doesn’t stop there, however. So many diseases result from cellular deficiency – Alzheimer’s disease, Parkinson’s disease, macular degeneration, Type-1 diabetes, Osteoarthritis, and on and on – all of these diseases share one critical problem which is a deficiency of cells. We can now make all of these cells from stem cells.
But lessons from regenerating the heart will extrapolate to these other areas and they’re going to greatly accelerate progress all of these other organs.
So I envision a time, maybe a decade from now, where a patient like my mother will have actual treatments that can address the root cause and not just manage her symptoms. I think we’ll have meaningful treatments for patients with heart failure or perhaps with Parkinson’s, macular degeneration and other diseases. This all comes from the fact that stem cells give us the ability to repair the human body from its component parts.
In the not-too-distant future, repairing humans is going to go from something that is far-fetched science fiction into common medical practice. And when this happens, it’s going to have a transformational effect that rivals the development of vaccinations and antibiotics.
Thank you for your attention.