Propelling Gene and Cell Therapy to New Heights for Patient Care: Q&A with Dr. Roger Hajjar, New Director of the Gene and Cell Therapy Institute at Mass General Brigham
Roger Hajjar, MD, who recently joined Mass General Brigham as director of the Gene and Cell Therapy Institute, has devoted his career to cardiac gene therapy research. His work has culminated in several clinical trials, and the scientific techniques he’s developed are utilized by investigators around the world.
In this Q&A, Dr. Hajjar discusses the evolution of gene and cell therapy over the course of his career, where he sees the greatest potential for patient benefit, and what excites him the most about joining Mass General Brigham to lead this unique program.
Q: What drew you to gene therapy research?
I completed my bioengineering degree at Johns Hopkins University, where I was very interested in muscle mechanics. Afterwards, I came to Harvard Medical School in its Health Sciences & Technology program, where I focused my research on why cardiac cells in a failing heart have severe dysfunction. This was the early era for heart transplants, and I studied cells explanted from the hearts of patients undergoing the surgery. We discovered how different proteins and molecules like calcium within the cardiac cell were deficient, and I used gene transfer technology (introducing new genetic material into cells) to validate these findings. That began my intimate interest in gene therapy.
Around this time, I was completing my fellowship in cardiology at Massachusetts General Hospital, focusing on heart failure. Seeing how my patients, especially younger patients, had such few options for treatment motivated me to find a way to translate the discoveries we made in the lab towards new therapies. Gene therapy offered an approach that might effectively deliver novel therapies into the heart to target and repair these cellular and molecular deficiencies causing heart failure.
Q: What studies have you conducted in the gene and cell therapy space?
My goal was to develop gene transfer methods that would effectively deliver a therapeutic solution to the failing heart. For many years, I focused my research exploring different gene therapy vectors that might accomplish this goal. Some of my initial discoveries made during my long tenure at Mass General are now used in cardiac gene therapy clinical trials today.
Specifically, we developed a gene transfer method to target calcium cycling (the release and reuptake of calcium in heart cells that drives muscle contraction and relaxation) in failing hearts, which has led to the initiation and recent completion of early first-in-human clinical trials in patients with advanced heart failure. That trial is now being conducted internationally.
Q: How has gene therapy evolved as a field since you began your research career?
Twenty years ago, there were many doubts about gene therapy, but I and fellow scientists forged ahead and worked on developing techniques and new vectors to target genes safely. At that time the main delivery method we used was an adeno-associated virus (AAV) vector, a harmless virus that we use to transport new genetic material into a cell.
In the years since, gene therapy has become more sophisticated and mainstreamed. I have watched some of these discoveries go from bench to bedside. These advances have enabled gene and cell therapy to be in the mainstay of treatment for a number of diseases. Increasingly, newer gene therapy approaches like CRISPR are being tested to edit genes that are too big for traditional AAV gene therapy.
Gene and cell therapies are now really at the cusp of a major turn; some of us think we've already made that turn.
Q: What diseases are gene and cell therapies used for?
There have been gene and cell therapy breakthroughs for a number of diseases. Very recently, a new gene therapy was approved to treat adults with hemophilia. We have also seen life-changing gene therapy treatments for spinal muscular atrophy (SMA). Gene therapy is also being used to treat inherited retinal diseases, where researchers can target a genetic mutation that leads to blindness through AAV-based gene augmentation therapy.
With cell therapy, major advances have been made for treating liquid tumors like lymphomas or leukemias. Autologous CAR-T therapy has made a huge difference in patients’ outcomes, providing new therapeutic options for patients who were resistant to second and third-stage treatments. There are many patients who had failures with their chemotherapy or bone marrow transplants who are getting cured by CAR-T, which has been an amazing development to witness.
Today, there are more than 25 gene and cell therapy products including cord blood-based treatments approved by the U.S. Food and Drug Administration (FDA), and many more are currently in early stages of testing.
Q: What do you envision for the future of gene and cell therapy treatments for patients?
I envision a future where we can offer gene and cell therapy to the many patients who have had few options until now. At Mass General Brigham, and throughout the field, there are clinician-scientists who are extremely motivated to find treatments for their patients, and that is what is going to propel gene and cell therapy forward. It is scientists’ dedication to their patients, to something essentially human, which propels their desire to offer them treatments, and thus find new solutions. There are developing treatments for devastating diseases such as aggressive glioma tumors in the brain. Every time you lose a young patient with these types of diseases, a part of you breaks. And if that's not a motivation, I don't know what is.
The ways to tackle these diseases are by using innovative, out-of-the-box thinking. Sometimes, as scientists, we're penalized for thinking too much outside of the box, because you always want to build on what's been known before. The failure rate for thinking out of the box is higher. But we need novel thinking to permeate throughout our work. Failure at the lab bench doesn't mean that you didn’t learn something from it; it just means that you need to take a different path, or you must engage another way of looking at the experiment or conduct new experiments.
Q: What excites you the most about taking on this new role as director of the Gene and Cell Therapy Institute at Mass General Brigham?
The Gene and Cell Therapy Institute at Mass General Brigham fills a gap in a way that is not present in the biotechnology industry or elsewhere. Within the Mass General Brigham system, we have this very deep knowledge base of the molecular and cellular mechanisms of disease, coupled with investigators who have validated these biological targets. On the other side of the spectrum, we have very motivated leading clinician-scientists, who want new treatments for their large patient populations. Merging these two forces, the early discovery with the clinical knowledge of disease, can help us achieve breakthroughs for patients.
We are very bullish about the large number of biological targets that Mass General Brigham scientists have identified. We feel that gene and cell therapy is a great platform to translate those targets into tangible therapeutic products for patients.
Every clinician-scientist within Mass General Brigham is really fortunate because of the vast spectrum of knowledge they can tap into. This is what sets Mass General Brigham apart – we have these motivated clinician-scientists who will work tirelessly to find their patients solutions.
Q: What are your goals for the Gene and Cell Therapy Institute at Mass General Brigham?
There is a crater in the gene and cell therapy field between early discoveries and first-in-human treatments. Our main goal within the Gene and Cell Therapy Institute at Mass General Brigham is to identify different molecular targets that can take advantage of gene and cell therapy platforms or use gene and cell therapy as a vehicle for treatment, and then deploy them towards specific diseases.
We are going to accomplish this by using our unique infrastructure to our advantage. We will work with individual investigators with specific treatment targets and conduct preclinical studies utilizing regulatory strategies to enable us to translate these therapies and start healing patients. We will create manufacturing capabilities to support preclinical and clinical studies to bridge the gap between interesting and potentially life-saving targets and eventually delivering treatments.
We will work in a systematic way where our scientists will partner with Mass General Brigham Innovation and key clinical leaders who will operate together to evaluate new treatment targets and assess their feasibility. Once identified, we will leverage the expertise of the Gene and Cell Therapy Institute behind them to translate them into first-in-human clinical trials. It is exciting to be able to work with these leaders in scientific discovery and clinical care and it affords Mass General Brigham a unique opportunity to make major differences for patients.
My framework has always been “bench to bedside,” and Mass General Brigham’s Gene and Cell Therapy Institute is a synergistic tool to do this with a high level of expertise and way of keeping the patient at the center of it all. The spotlight in on healing patients, we are simply the vehicle for getting there.
