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Gene Therapy to Treat Damaged Heart Tissue

Todd Herron, Ph.D., assistant research professor in the Department of Molecular & Integrative Physiology at the University of Michigan in Ann Arbor, talks about his research involving gene therapy to treat damaged heart tissue.

How can the gene transfer help heart failure patients?

Dr. Todd Herron: What we're hoping to do is to eventually be able to deliver genes directly to a failing heart. Currently, the best therapy is heart transplants for heart failure patients, so our goal would be to increase the quality of life of patients by transferring genes into their hearts that would make their heart contract more powerfully.

Would this process be for any patient with heart failure?

Dr. Herron: Yes, the potential clinical application of this research would be to inject a virus into the heart, ideally through a vein – a peripheral vein in the leg – and hopefully if we could engineer one, the virus would travel to the heart, turn on its expression, and then be permanently expressed in the heart.

How does the process work?

Dr. Herron: We've used molecular biology strategies. We've cloned a full-length human gene and we've engineered a virus to express that gene. This gene that we isolated is for the heart's motor, the molecular motor that is responsible for each contraction. When someone has a failing heart, it's being reported that only a slow motor is expressed, whereas in a normal heart, there is some expression of a fast motor, so we isolated the fast motor gene and then we expressed that fast motor gene in failing heart cells in vitro from a genetic engineering technique in the laboratory.

How quickly would it take for the heart to start pumping regularly?

Dr. Herron: In the in vitro experiments that we did, it was after two days of treatment with the virus that failing heart cells began to contract with more vigor, so they had faster contraction and a greater extent of contraction.

When you get to the stage that you try this in people, how often would they need to get a gene transfer?

Dr. Herron: One of the limitations currently with the gene transfer technology is that now the most efficient viruses and most efficient gene transfer methods are transient. We're working in the lab to design better, more efficient gene transfer techniques so that we would be able to turn a gene on and have it expressed throughout the life of a patient.

Would it basically be one shot in the leg to get the heart pumping?

Dr. Herron: Ideally, yes, that's the ultimate goal for our research.

What have been the results of the lab research so far?

Dr. Herron: Our studies in the lab have been mostly in vitro studies. We've identified a candidate gene that when we express it in heart cells, it causes the cells to contract with more force and to contract faster. Our next step is to start putting this gene into animal models of heart failure and then to see if there's any in vivo therapeutic benefit of injecting this gene into the heart.

How long will it be before you start testing this on humans?

Dr. Herron: Quite a ways. It's hard to put a number on it. There has to be extensive research done in animal models of heart failure before we can think about testing this in humans.

What kind of virus are you attaching the gene to?

Dr. Herron: In the study that we published, the gene was inserted into an adenovirus, which is a virus that causes the common cold, so it's a very common virus. One of the limitations of that virus is that it causes an immune response, so we need to find other, more therapeutically relevant viruses. There is a relative of the adenovirus called adeno-associated virus, which has more therapeutic benefit.

If you use the cold virus and it causes an immune response, does it make the antibodies attack the heart?

Dr. Herron: Yes, exactly, that's it. Currently, the most efficient viruses for gene transfer are also associated with the high immune response, so we have to make it so that doesn't happen.

How many open heart surgeries and heart transplants would be avoided by using this gene transfer?

Dr. Herron: I can't put a number on it, but ideally, it would be a new therapy for heart failure patients so that they wouldn't have to get a heart transplant.

How did you get started on this path of helping failing hearts?

Dr. Herron: I got started on this path when I did my Ph.D. research. My Ph.D. research focused on the molecular motor in the hearts. Ever since then, I guess I became somewhat obsessed with studying that protein. While I was studying it, there were reports that came out indicating that in heart failure, there is a loss of the fast molecular motor, so the hypothesis in the field has been that replacing that fast motor in the failing heart may increase its function.

Could this be used in the future to treat heart arrhythmias?

Dr. Herron: It does have the potential to treat a variety of genetic-based diseases, such as arrhythmias, yes.

Do you think this is the next step for heart therapies?

Dr. Herron: It could be. It could be a big next step for heart therapies. It would be a more non-invasive method for treating heart disorders.

What happens exactly during the process?

Dr. Herron: Ideally, we would be able to inject a virus systemically, say through a leg vein, and then using molecular genetic tools. Hopefully, we can design a virus that would be targeted directly to the heart, rather than to other organs in the body. Once that virus would reach the heart, it would release this genetic material, and then by putting a therapeutically beneficial gene into the virus, that would turn on a beneficial gene in the cells of the heart. Hopefully, it would make it pump stronger.


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