Natalia Trayanova, Ph.D., a biomedical engineering professor and Murray B, Sachs Endowed Chair at John Hopkins University in Baltimore, Maryland, talks about a new, gentler technology that could replace defibrillators when shocking hearts back into rhythm.
Interview conducted by Ivanhoe Broadcast News in September 2016
.What is the term optogenetics, what is the field and what are you looking at?
Dr. Trayanova: Optogenetics is an emerging technology by which the electrical functioning of the cell is modulated. These are cells that have been made to express light sensitive channels and the light sensitive channel, when illuminated, can pass electricity and change the electrical functioning of the cell.
Is this used commonly in research?
Dr. Trayanova: It’s an emerging technology; it has initially been developed for studying the brain and the neuronal behavior. Recently inroads have been made with implementing the same technology in the heart. It’s in fairly early stages.
With that background in mind you’re looking at light, can you tell me what it is that your lab is looking at in conjunction with Bonn?
Dr. Trayanova: We have been working on trying to figure out how we can use optogenetics to affect cardiac electrical function. One of the most important uses of electricity in treatment of heart disease is to defibrillate, which is to terminate disturbances in heart rhythm that lead to sudden cardiac death. Patients who are at risk of sudden cardiac death typically receive implantable defibrillators. Those are devices that would deliver a very high energy shock and shock the heart out of its electrical dysfunction. Patients who have these devices implanted experience major discomfort during the shock. It’s very painful; also they are often inappropriate shocks, which mean the components of the device are malfunctioning. While it is a lifesaving technology, it isn’t really something people would like to live with in the long term. A very important avenue of research is to figure out how we can develop better technologies to terminate these life-threatening disturbances in heart rhythm and prevent sudden cardiac death, which has claimed so many lives and particularly the lives of many young people in the prime of their life.
You’re just in the beginning stages of looking at this. I know researchers at the University of Bonn, Germany, with whom you collaborate, are using mouse models to address the same question. Can you describe what is going on with the research, where are you at?
Dr. Trayanova: Just to give a little background, my lab is called computational cardiology lab and we are working on creating models of the functioning of the heart. We refer to our models as virtual hearts, because we take cardiac images from patients and we construct their individualized hearts, and we can model the electrical properties of the heart of an individual patient. In this project, we use the expertise that my lab has in creating patient heart models and we try to figure out whether in these models we can deliver light and terminate the arrhythmia that these patients have. The group at Bonn University conducted the experimental component of this research. They did experiments in mice in which they imbedded light sensitive proteins and then delivered light from the outside of the heart. They were able to defibrillate the heart, to terminate the arrhythmia. In my lab we did a parallel approach in which we used patient heart models. What we did is to provide the bridge from what is experimental to what potentially can be done in the clinic. Of course we are far from the latter but we are channeling the experimental research in the particular direction to reach a point in which this will be clinically implemented.
At the University of Bonn they use light to defibrillate mouse hearts?
Dr. Trayanova: Mouse hearts, exactly.
And they were successful?
Dr. Trayanova: They were very successful. The researchers did it in transgenic mice initially — those are mice that already have the protein expressed. Then then they did it in mice hearts in which they embedded the protein later when they took the heart out.
Your lab is conducting the research in a virtual way, not in an actual heart?
Dr. Trayanova: It is a model of the heart but it’s a very realistic model because it is based on the MRI scans of a patient who had an infarction. A patient who had come to the hospital to get a defibrillator implanted. We took this patients MRI scans and developed a heart model. Then we asked the question: if this patient would not have gotten a defibrillator implanted, could we defibrillate that heart with light?
Again you would be, and this is down the road, potentially looking at an implantable device and then red light will be delivered from the outside? How would that work?
Dr. Trayanova: The way we envision the practical implementation is that it will be a device that is implanted in a fashion similar to the implantable defibrillator; the difference is that light does not cause pain, while electrical shocks cause pain. There will be a sensing electrode, which will determine whether the heart has an arrhythmia and if it does, and then the light pulse will be delivered.
Obviously there’s a lot of research yet.
Dr. Trayanova: Yes, on the technology side. What we demonstrated is a proof of concept, feasibility of optical defibrillation, feasibility of delivering the light to affect cardiac function. The technology side — exactly where and how the device will be placed, how the light will be delivered, that needs to be worked out. We now know, however, that it is possible, and that was the crucial point of the research that we did in collaboration with the group at the University of Bonn.
How far down the road until we could see this as a reality?
Dr. Trayanova: Of course it’s very difficult to answer this question. Our initial estimate, which we made when we published our first big paper on modeling optogenetics, was probably ten years. Well it’s been three years since then. Sometimes research moves very fast and while I can’t put a number of years I must say the steps that have done in the last few years are major. This is a major milestone. Maybe in a few years, maybe further, but the major milestone is here. The approach is possible, and from here on we have to work out the technology.
Is there anything else from an overview of big picture sense that I didn’t ask that you want to make sure people know?
Dr. Trayanova: Because when one conducts an experiment, it is difficult to tell when the light enters the heart, how it interacts with the cells, how exactly termination occurs. You can’t uncover this by looking at the mouse. By dissecting the model, slicing it, looking at the activity of each cell, we can say what the mechanism is. It’s an important contribution. Our contribution in this research was not only the feasibility of the optogenetic defibrillation approach in a more clinically realistic situation — a real patient with a real problem — but also understanding how exactly termination of arrhythmia by light occurs. That’s number one. Number two, by doing the virtual heart simulations we are able to channel future experiments. We are able to say, don’t go ahead and explore all this parameter space, all these possibilities in the experiment, what kind of light should be used, how long the pulse would be. We can do that in the simulations — you don’t need to do more experiments to answer these questions – we can do that. We see our simulation research as bridge to the clinic in terms of feasibility, as a mechanistic understanding of what is happening and finally as a guideline, where to go with the experiment: how to narrow down what the future investigations should be, how to not waste resources in terms of mice, etc. and what would be the most productive path forward.
When you were talking about the current defibrillators that are implantable, if it does happens to go off you mentioned it’s in innocent bystander until it’s needed?
Dr. Trayanova: Yes.
People have said once it goes off that’s—-
Dr. Trayanova: The shock is very painful. Yes defibrillators are generally I would say quite uncomfortable to live with; it’s just the constant fear that it might discharge. If it discharges then it’s very, very painful and feels like a horse is kicking you in the chest and people can lose consciousness. Also a lot of people who have defibrillators would have psychological problem just from the fear and the experience. In addition there are studies that show it increases mortality, damages the heart. It is a lifesaving technique but it’s quite imperfect. What we say normally is, if you want to open the door and you don’t have a key, you use a bomb to open it. This is that kind of technology, it’s a blast to the heart to solve the problem, because we don’t know how to do it better, in a more gentle and mechanistic way. When you know exactly what’s happening, then you can figure out how to fine-tune it, but we haven’t gotten to that point. Optogenetics opens a new avenue for fine-tuning the rhythm of the heart and that’s why we’re so excited about it.
END OF INTERVIEW
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