Dileep R. Yavagal, MD, Professor of Neurology and Neurosurgery, Faculty Member of the Interdisciplinary Stem Cell Institute, Director of Interventional Neurology and Co-Director of Neuroendovascular Surgery, University of Miami Health System, talks about stroke patients and clinical trials using healthy donor stem cells to help stimulate growth and repair in a stroke patient’s brain cells, aiding in recovery.
Interview conducted by Ivanhoe Broadcast News in December 2017.
Let’s start with stroke itself, do we know how many people are affected by stroke every year and can it happen to anyone?
Dr. Yavagal: Absolutely. We have actually very detailed statistics over several decades now of the burden of stroke. It’s close to eight hundred thousand Americans every year that suffer from stroke and it’s the leading cause of disability in the US, and the top reason for people either in wheelchairs or in nursing homes.
What happens with a stroke basically?
Dr. Yavagal: The most common kind of stroke is a sudden blockage in one of the arteries in the brain cutting off blood flow to that part of the brain. The brain is the computer that runs the body and that part of the computer shuts down. If you were to think about a robot being run by a computer, if one part of the circuit shuts down, the part of the robot controlled by that circuit stops moving. Similarly, in a stroke, one part of the brain shuts down and a person most often gets paralyzed on one side of the body. The other big things that can happen are that speech can be slurred or lost eyesight can also be affected; typically only one side of the vision because this is again due to only a part of the brain vision processing area being affected. Additionally, one can experience sudden loss of balance and double vision. This symptom complex all comes on very suddenly, that’s the hallmark, and that’s why the term is stroke. The less common type of stroke, which is about fifteen percent of all strokes, is a sudden bleeding in the brain. That can happen because of high blood pressure where your arteries suddenly burst. And even less common is an aneurysm, that’s a bubble on the artery bursting in your brain. The total burden of stroke in the US due to loss of productivity and disability, and together with the treatment costs are estimated close to thirty billion per year.
Thirty?
Dr. Yavagal: Three zero, yes.
So astounding numbers.
Dr. Yavagal: And a number that really needs to be tackled by reducing stroke disability.
How important is it to recognize the symptoms of stroke, is there a window there that is critically important?
Dr. Yavagal: Absolutely. The big news from the last three years is that if a person suffering from a stroke is brought to a stroke center within six hours we have almost a seventy percent chance of reversing the disability with a treatment called mechanical thrombectomy that we and other comprehensive stroke centers perform 24.7. It’s a catheter-based surgery where we go up into the brain and unblock the blockage emergently. So that’s one of the big reasons that stroke symptoms should be recognized right away, it should be a very low threshold, because if you’re wrong nothing is lost but when you’re right it’s a difference between being disabled or not.
Exactly, and in many cases like you’re saying as in Julian’s case when it’s not really recognized right away and time passes that’s when debilitating symptoms can—
Dr. Yavagal: Can really remain and it’s really hard to reverse them or improve them after the first few hours. We have some benefit from rehab and then we are trying these new therapies that we are doing research on like for Julian. But as of now in terms of approved treatments we have the clot-busting medication called tPA and the mechanical thrombectomy to offer if they’re within the first few hours.
So now when we mention some of these others things that you are researching here tell us about the stem cell study, the clinical trial and what you’re looking at here.
Dr. Yavagal: Absolutely. Just to give a quick background on the stem cells, these are the building blocks of our bodies that fortunately for us are present even when we become adults. And they’re present in different tissues including the bone marrow and the fat tissue. They can also be derived from the umbilical cord after pregnancy, from the placenta, and the teeth actually. But the most common source of these adult stem cells is the bone marrow and that’s what we are using in this study called the ACTIsSIMA trial.
ACTIsSIMA trial and you are taking the stem cells really from the patient’s own bone marrow?
Dr. Yavagal: No.
No that’s wrong please clarify doctor. Where do the stem cells come from?
Dr. Yavagal: So these are pretty ground-breaking stem cells in the sense that they are from healthy donors. And so it’s really a cell transplant from healthy donor into the patient. The biggest astounding fact is that because they are stem cells and not fully formed organs they don’t need immunosuppression. They don’t need any strong drugs to bring down the patient’s immune system for us to be able to give it to them. We just give it to them like a blood transfusion. I mean the technique is a stereotactic technique, but just like you don’t need drugs to be given to suppress the immune system for a blood transfusion, these act the same way where in healthy donor bone marrow cells can be given whenever we have a patient. We don’t have to wait for the process of getting them from the patient and processing them or anything like that. These are ready go and that’s what we used in the study.
So the donors donate the blood marrow stem cells?
Dr. Yavagal: Bone marrow.
And tell us how the trial works like in the case of Julian. What is the criteria for the patient, what you’re looking for and then how that works when they get the procedure?
Dr. Yavagal: So the trial is intended to research if we can improve the neurologic deficits – the physical deficits from a stroke in the chronic phase of the stroke. This trial is geared towards making a motor deficit better, for whichthe M in ACTIsSIMA stands. At least six months out but within seven and a half years from the stroke is one of the major criteria. The other main criteria for patients to be eligible for this trial is have to have either an arm or a leg quite severely weak from the stroke. There is also an age range of eighteen to seventy five. Then there are other criteria to make sure that there aren’t any other life threatening conditions and things like that, which could exclude them. The patient also has to be able to get this stereotactic procedure that is used for administration of the cells. I can talk about the procedure briefly. If the patient meets the screening criterion, which includes an MRI to verify that the stroke site is less than a hundred and fifty ml volume, then we can administer cells in the surrounding brain tissue that is damaged but not dead. So it can’t be a very, very, very large stroke because we have to have enough salvageable brain around for the stem cells to help re-establish circuitry. The way the stem cells are administered in this trial study is that they are given sterotactically, meaning that we use a brain GPS system, which is a mechanical system that has very precise ways of delivering small pipes through small holes into the area of the brain that is affected. That is what our neurosurgeon does for us to administer these cells. The cells are placed around the stroke area with the idea that the cells will stimulate repair of the stroke area.
There are other trials where stem cells are delivered in a different way, through different routes like the vein or into the carotid artery using catheters … But in this study the cells are given directly into the brain with needles.
To stimulate repair is it to regenerate? And you said to get the circuitry—-
Dr. Yavagal: Yes. The thing that we learned over the last decade or so is that the adult stem cells actually don’t form new brain by themselves. However, they enhance the brain’s ability to repair itself. They stimulate what’s called endogenous neurogenesis, which means that they stimulate the brain’s own growth. And thereby reintegrate the damaged circuitry, form new circuitry and actually after some time they seem to be thrown out by the body. So they act more like drug factories that have a lot of very good chemicals that are used in repair. By administering them near the stroke area these live stem cells secrete the chemicals in the injured area and enhance the body’s own repair mechanisms, which are often very limited especially in the chronic phase of stroke.
So what would you hope to see when it comes to a patient like Julian, he’s a couple of months out but what would you hope to start seeing if he received the stem cells?
Dr. Yavagal: Yeah, that’s a good question. We have very objective, very strict measures of strength that we hope to see an improvement in along with a host of other measures like the cognitive measures, the ability to think about tasks and also just perform activities of daily living. But the big changes that we are looking for are the motor improvements in the weak limb or weak limbs. We will be measuring them with the help of our rehab doctors who are very, very skilled at measuring these changes, so that we don’t have just a subjective idea that things have improved but we actually have a very precise measurement of the motor improvement. We are also doing MRIs with very sophisticated techniques to see if the fibers that are involved in the circuitry show any improvement. It’s called DTI sequence imaging. So we are using multiple measures to see if the patient in this trial who indeed did get the cells clearly do better than the ones who didn’t. And we examine patients first at one month, then at three months, then at six and twelve months post-surgery.
You could still enroll in this trial?
Dr. Yavagal: No. The trial is now closed for enrollment. However, it is possible that a phase III will open in the future, but we don’t know this yet. Additionally, we do have another stem cell trial opening soon for chronic stroke. It is very similar to this study but it will investigate a different type of stem cell.
Then the final goal or ultimate goal with hope to be that if this works get it into doctor’s hands I suppose?
Dr. Yavagal: That’s absolutely the ultimate goal. And in fact the FDA has put a special focus on cell-based therapies that they call biologics. These area broad family of therapies to really accelerate the pathway to get these cells into doctors’ hands. Typically we would do what is called a Phase III trial after this, but I think there are good chances that we will accelerate the pathway making it accessible faster than usual. That’s definitely the goal and the thing I do want to mention is that the buzz of stem cells has been there now for almost two decades or a little more but the hard evidence necessary to actually start offering it to patients is still lacking. And this is the kind of science that clinical trials offer – they will give us that data to confidently offer treatment to our patients on a wide scale.
END OF INTERVIEW
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