Jean-Antoine Ribeil, MD, PhD, recently joined Boston Medical Center’s Department of Hematology and Oncology as clinical director of the Center of Excellence in Sickle Cell Disease. As an internationally- renowned hematologist who has worked in both clinical and research capacities, Ribeil brings an expansive and comprehensive background in sickle cell disease (SCD) to BMC.

BMC’s Office of Development recently spoke with Ribeil to discuss his dedication to patients with SCD, his contributions to advancing the care, therapies and research of the disease and his vision for deepening that work at BMC.

Boston Medical Center (BMC): Can you tell us a bit about your background?

Jean-Antoine Ribeil MD, PhD (JAR): I’ve always been interested in the biology of red blood cells so after completing my training as a hematologist, I pursued a PhD to study erythropoiesis [the process by which mature red blood cells develop from stem cells].

I worked at Necker Hospital in Paris, [France], which mainly serves pediatric patients but also has an adult patient population. There was a huge pediatric clinic for SCD but nothing really for adult patients. With the help of the pediatric team, I developed and led a sickle cell program for adult patients that served the western part of Paris. I focused on the transition from pediatric SCD care to adult SCD care. In addition, I established a national reference center for pregnant women with sickle cell disease.

During my time at Necker Hospital, we started a gene therapy program for hemoglobinopathies. We performed the first gene therapy for a patient with SCD using the transplantation of autologous hematopoietic stem cells that were genetically modified. After successful results, the sponsor of the study, Bluebird Bio, offered me the opportunity to come work with them directly to obtain similar results in the United States and Europe. While it was a difficult decision to leave clinical practice, I felt it was important to continue the development of gene therapy programs for SCD to ensure that these protocols were headed in the right direction.

After achieving improvements in gene therapies during my time at Bluebird, I decided it was time to return to clinical practice. I would also like to develop the next generation of gene therapy, where it is available to as many patients as possible with less of a burden on them. That led me to Boston Medical Center, because I felt it was the perfect place for this work.

Why is Gene Therapy Important for Sickle Cell Disease?

Sickle cell disease (SCD) is an autosomal recessive genetic disorder (inherited from both parents), caused by a specific mutation in the beta-globin gene. It leads to production of an abnormal strain of hemoglobin (a protein in red blood cells that carries oxygen to organs and tissues and brings carbon dioxide from organs and tissues to the lungs) called Hemoglobin S (HbS). Normal hemoglobin is always soluble, meaning it can be dissolved, in the red blood cells (RBC), but HbS hemoglobin forms rigid polymers upon deoxygenation or other stress—for example, dehydration, fever, etc. In turn, the intracellular, meaning occurring within the cells, formation of HbS polymers results in deformation of the RBC into the characteristic sickle shape that decreases its flexibility and is responsible for chronic hemolytic anemia and acute microvascular vaso‑occlusions or infarctions. This results in acute life-threatening conditions, chronic multiple organ damage and premature death.

The Centers for Disease Control and Prevention estimates 90,000 to 100,000 people are affected by SCD in the United States. Given the intensive management needed to improve survival and care for these patients, this represents a significant public health burden.

The fetal hemoglobin (HbF), expressed in fetal life and the first month of life, prevents polymer formation and has anti-sickling activity. However, HbF is normally present at too low a concentration in adult subjects with SCD to influence clinical symptoms. Symptoms of SCD can begin as early as a few months after birth as the level of fetal HbF decreases. The concept of gene therapy in sickle cell disease is to induce the production of anti-sickling hemoglobin to dilute HbS and prevent the HbS polymerization and the RBC’s sickling that induces vaso-occlusive events and hemolysis.

BMC: What drives your passion for this field?

JAR: I am passionate about this field because I was completely moved by the patients and the challenges they and their families go through because of SCD. I feel it is my responsibility to improve care and treatments so we can help people. Any of my new ideas for research and new treatments always come from my interactions with patients. That’s why it is so important for me to go back to clinical practice—to have these conversations and continue to understand and advocate for the patient. Everything circles back to achieve the goal of helping patients.

BMC: What drew you to Boston Medical Center, especially the Center of Excellence in Sickle Cell Disease?

JAR: You can see a difference between BMC and other academic medical centers. When I met the team and heard them talk about their work, I could see how much they care for the patients. I immediately saw BMC’s commitment to exceptional care, without exception—that was my mindset already and it was immediately clear the team felt the same way.

I also appreciated how the Center of Excellence in Sickle Cell Disease is integrated within [the Department of] Hematology Oncology. That will help develop a culture of caring for SCD patients across all specialties and areas and to all doctors, nurses and team members.

BMC is unique because it is the largest sickle cell center in New England, having pediatric and adult care under one roof so we really can provide lifelong care and optimal transition planning. Also, BMC focuses on social determinants of health and is conducting world-class research. An organization offering all these aspects in the one place is pretty rare in the world—it’s a health care organization for all phases of life, from birth to adulthood.

BMC: What makes BMC a great place for developing SCD care and therapies?

JAR: There are not many treatment options for patients with SCD and there are no curative options for most of the patients. As a medical doctor, I want to change that. The pain and struggles patients go through is unfair and it makes me want to do more and work harder. I want to give more options to my patients. My hope is 10 years from now, gene therapy will improve greatly and will be available for most patients.

These goals start with the academic research and expertise we are setting up here at BMC. We will have a clear strategy and plan and bring the best care and innovative treatments to everybody. We will ensure the clinical trials we host and our own research will be beneficial to patients. At BMC, we’re not just conducting science for the beauty of science or recognition. It’s about having a positive effect on patients and their families—in Boston and beyond.

BMC: In your role as clinical director, what do you hope to bring to the sickle cell program and our patients? What are your areas of focus?

JAR: My vision looks a lot like a pyramid and all of the layers are interconnected.

At the base, we are focused on transition of care to build greater communication between team members and organization of care. SCD is a disease that destroys all the organs and the first symptoms start between six and 12 months of age. That’s why transitioning care from the pediatric clinic to the adult clinic is invaluable—chronic complications start at pediatric age, and having a seamless transfer improves care and helps prevent complications.

Working hand-in-hand with the pediatric department—I am in charge of the adult clinic—we will focus on the collaboration between teams and help patients feel empowered in their care and trusting of their medical teams. When patients know their providers have their best interest in mind, it helps with better uptake of innovative treatments like gene therapy.

The next layer is clinical trials. Access to trials improves the quality of patient care. We need patients to feel comfortable with the idea of clinical trial participation. We will be selective about which trials we accept and we need to show pharmaceutical companies that we are equipped and organized for trials.

At the top of the pyramid is institutional research.  As an academic medical center, using the experience gained with the current gene therapy programs we will be able to set up programs and put our best science forward for the patients affected with various diseases.

Our new biobank program allows us to collect data about the SCD patient to better analyze their disease in a longitudinal way. The opportunity to see how patients are evolving over time is rare. This will also allow collaboration with international groups.

BMC: It’s clear you operate with a patient-centered mission. Why is that so important, and how is that reinforced at BMC?

JAR: Interactions with patients inspire ideas to develop better treatments—they are at the forefront of everything we do. The fact that BMC’s laboratories are integrated with clinical care is the ideal type of translational research and medicine because it means we can reach patients that much faster with new and improved care. Helping make that happen are the incredible experts, specialists and researchers at every step of the process who share the same focus on patient care and research prospects—that type of integration is rare and needs to be cultivated, emphasized and preserved.