How and why Louisville became an epicenter of cardiovascular stem cell research.

By Atul R. Chugh, MD

As we say goodbye to events that define Louisville’s position on an international stage with celebrations such as the Kentucky Derby, Thunder over Louisville and various other arts and social happenings, I am almost embarrassed to admit that before moving here, I had no idea that these even took place in Louisville. (The Kentucky Derby was a toss-up between Louisville and Lexington.) As a physician-in-training focused on emerging research, Louisville was only synonymous with one thing to me: cardiac regenerative therapies.

For many years, Dr. Roberto Bolli and his team had been recognized in the scientific community for spearheading some of the most pivotal cardiac stem cell studies in animals. The studies showed the ability of an animal’s own cells to regenerate parts of the heart damaged by laboratory-created myocardial infarctions. The strength and novelty of this work prompted me to apply for my cardiovascular medicine fellowship in Louisville, and I was very fortunate to be accepted. Since then, I feel honored to be a part of our clinical work with Phase I stem cell studies.

Joining the CCTRN
On the basis of our work in this field, Dr. Bolli and his team were asked to be a part of the Cardiovascular Cell Therapy Research Network (CCTRN), a small but very prestigious group of researchers funded through the National Heart, Lung, Blood Institute (NHLBI) and tasked with developing and performing cutting-edge clinical trials to investigate the potential advancement of cardiac regenerative therapies.

Aside from just focusing on the safety and efficacy of these approaches, a great amount of effort is spent on understanding mechanisms, the methodology of trial design and measuring the changes attributed to the therapies using state-of-art techniques such as cardiac MRI, PET and cell labelling. The Network, at this time, focuses on adult cell types which allow us to harvest cells, often times, from the patient herself undergoing the therapy. The objective is to find circulating cells that have the ability to regenerate parts of the cardiovascular system damaged by disease.

Who’s Who of Researchers
Within the Network resides a veritable “who’s who” of researchers considered to be world-class leaders in their given fields. Of note, this consortium includes the following medical centers: Stanford University, Minneapolis Heart Institute Foundation, Texas Heart Institute, University of Florida, University of Miami, Indiana University and the University of Louisville. The Coordinating Center is housed at the University of Texas School of Public Health in Houston. As the proverbial new kid on the block, interacting with the members of the CCTRN, for me, is akin to sneaking into a celebrity-charged, ultra-exclusive Derby party. Having just returned from our semi-annual face-to-face meeting in Houston, the experience of the inner workings of the Network are very fresh in my mind.

After a grueling day of trying to refine the protocols of the studies that we are currently working on, it was surreal to be having a drink with Dr. Doris Taylor, who I just saw on 60 Minutes a few weeks ago. It is, however, equally stressful, having a difference of opinion with the likes of Jim Willerson (the longest-serving editor-in-chief of Circulation) or Dr. Carl Pepine (a past president of the American College of Cardiology and a pioneer in the field). To illustrate the depth of talent, our coordinating center’s director, Lem Moyé, is not only a brilliant trialist and biostatistician, but also writes his own highly recognized works of fiction in his free time.

Quest for Answers
Antithetical to what one would expect from such talented figures, what I find most admirable in this Network is a true, unfettered quest for answers. Never have I worked with a group so wholly committed to a single goal: to find an alternative therapy for cardiovascular diseases, which currently have limited options in the cardiovascular realm. Egos are left at the door and everyone rolls up their sleeves equally.

What has been gratifying is how open and inviting the Network has been to the Louisville team. Dr. Bolli is now the head of the publications committee, which oversees the publishing productivity of the Network. I have been fortunate enough to play a leadership role in the developmental phase of a heart failure study which for the first time, uses a combination of cells for the treatment of heart failure. Additionally, Dr. Bolli is heading up the development of a new trial, which will hopefully focus on patients with heart failure secondary to chemotherapy used in cancer treatments.

Local Impact
Internally, the Network has been a catalyst for our partner, KentuckyOne Health and the University of Louisville to work even more closely by joining resources and adding efficiency to our research processes. The combined team has made great strides with an unbridled enthusiasm to perform well within the Network. Thus far, our selection into the Network represents, arguably, our greatest collective achievement in the arena of clinical and translational cardiac regenerative research.

While it would be easy to focus on the CCTRN’s benefits to the University of Louisville and KentuckyOne, I would argue that very few cities in the country need such a vehicle more than ours. Unfortunately, Louisville has made local and national news as a result of abysmal rates of hypertension, coronary artery disease and heart failure. As per the 2014 Louisville Metro Health Equity Report, cardiovascular death rates in Louisville are still above the national average, and these high rates are driven largely by co-existing risk factors such as diabetes, smoking, obesity and hypertension. It is imperative that a population with such high rates of disease have access to all available forms of treatment, both established and experimental.

This is where our involvement with the CCTRN is of great value for the community. The Network allows the community access to clinical trials and potential treatments in populations where other treatments are not feasible. For instance, in our patients with end-stage heart failure, options are limited to left ventricular assist devices and heart transplantation-two therapies where eligibility and feasibility on a large-scale would be challenging.

Of note, only 2,000-2,500 heart transplants have taken place in the U.S. yearly for the last 10 years due to a lack of a donor pool. Therefore, a very elegant solution to the problem would be to regenerate parts of the heart, which have already undergone extensive injury. This is what we have the opportunity to study and develop with our place in the CCTRN.

Current Trials
Currently, the University of Louisville and KentuckyOne Health have a trial through the CCTRN that is enrolling called the PACE (Clinical and MRImaging Assessments in Patients with Intermittent Claudication Following Injection of Bone Marrow Derived ALDH Bright Cells) trial. The study focuses on individuals with atherosclerotic (cholesterol plaques) disease of the legs and uses the patient’s own cells in hopes that they can ameliorate symptoms that arise from decreased blood flow to the extremities.

And, we are looking forward to bringing other studies from the pipeline to Louisville, which will be very novel studies in patients with heart failure, coronary artery disease and peripheral arterial disease. We anticipate one such study to be up and running in the next six months, with others following in quick succession.

Given these developments, it is an exciting time to be in Louisville. I hope that in the coming days, as we take pride in being Louisvillians sipping our mint juleps and singing along to “My Old Kentucky Home” at the races, we also think of our scientific achievements and associations.

One such association is our involvement with the CCTRN and with it, what the future holds for Louisville, both as an epicenter of research and as a city that offers its denizens cutting-edge therapies difficult to find anywhere else in the world.

Atul R. Chugh, MD, is director of advanced cardiac imaging and director of preventive cardiology for University of Louisville
Physicians and assistant professor in the department of medicine at the University of Louisville School of Medicine.