St. Jude explores curative therapies for sickle cell disease

‘Be Bold, Be Brave, Think Big’

Those words helped recruit Mitchell Weiss, MD, Ph.D., to St. Jude 10 years ago. Today he is chair of the St. Jude Department of Hematology and is helping lead the work St. Jude is doing to help children with sickle cell disease live longer, healthier lives. 

Q: Tell us a little about yourself Dr. Weiss.

A: I am a physician scientist, which means that I see patients and do research in the laboratory, and I try to apply my research for the good of patients. This involved a lot of training. 

I got an M.D. and a Ph.D. degree at the University of Pennsylvania, and then I went to Boston Children's Hospital and Harvard University, where I trained in pediatrics and pediatric hematology and oncology. And after some time there, I moved back to the University of Pennsylvania and the Children's Hospital of Philadelphia, where I stayed for about ten years before I came to St. Jude. 

I spent my career studying red blood cell development in the lab while seeing patients with blood disorders, many of whom had sickle cell disease. I came to St. Jude in July 2014 because I saw it as an opportunity to apply my research for the good of patients and in a greater capacity than I could do at most other places.

Q: What sets St. Jude apart from other children’s research hospitals? 

A: One of the reasons that I came to St. Jude was to expand my research from being mostly basic science to helping patients. And this involved two things that are required to “move the needle”. First, I was offered the opportunity to lead a multidisciplinary effort that includes many talented individuals, and second, I was offered the required financial resources.  

Research that impacts patient care is expensive, especially developing and conducting clinical trials. 

So, when I came to St. Jude, I did a few things with the goal of expanding our research in sickle cell disease. One thing I did was to change my own laboratory so that about half of the effort was focused on work that could eventually help patients.  

 I also began to recruit into our Hematology Department faculty and staff who could contribute to our effort to develop transformative therapies for sickle cell disease. For example, I recruited experts in genome editing and gene expression in red blood cells.  I collaborated with Dr. Stephen Gottschalk (Chair, St. Jude Department of Bone Marrow Transplantation & Cellular Therapy) to recruit a faculty member with interest in bone marrow transplantation and gene therapy for sickle cell disease.  In this way, I built a critical mass of multidisciplinary experts who could work within the outstanding St. Jude infrastructure to provide care and research for patients with sickle cell disease.  

Q: Why assemble this really impressive group of people to work on sickle cell disease, whether in the clinic or in labs?

A: Well, this is a terrible disease. Patients begin to suffer as children frequently with attacks of terrible pain that require going into the hospital. Sickle cell disease is associated with a shortened life span because there's chronic organ damage that gets worse over time. The average mortality age of people with sickle cell disease in the United States is about 45 years old.

Most patients also experience serious health problems, including stroke, heart disease, kidney disease, and lung disease. Sickle cell patients represent an underserved community, although there is a growing number of health care professionals who want to improve the care of those patients and develop new treatments using cutting edge science. 

Q: What is St. Jude doing to help generate more options for treatment and care for sickle cell patients?

A: We have a program called the Sickle Cell Disease Collaborative Research Consortium, which  funds scientists  from across the US to perform synergistic collaborative studies on sickle cell disease. Our consortium has experts in gene therapy, genome editing, red blood cell biology and mechanisms of gene expression who are working together to advance treatments of sickle cell disease. We've been very successful at a basic science level. 

For example, we have had several publications on new approaches to use genome editing to treat sickle cell disease and now  we are working to adapt those approaches to clinical trials.

This is something that we couldn't have done without the help of St. Jude and our donors because bringing together expert researchers from across the country to adapt their research toward a common goal is expensive.  St. Jude donor funds are supporting this research and these collaborations. 

Q: What are the implications of these collaborations in the next three, five, seven years? What could it lead to? 

A: Well, ideally, this work will lead to improved treatments for sickle cell disease, including genetic therapies and better medications.  

The early data on genome editing look very promising. But we need many more years of long term follow up to know that, and to be sure that there won't be long term toxicities. 

Looking forward, some of the consortium’s collaborative discoveries [about the regulation of hemoglobin expression] have illuminated new strategies for creating more effective drugs, and I expect they will be further explored. 

Q: What are the implications of the work you’re doing on a global scale?

A: Sub-Saharan Africa has the largest burden of sickle cell disease in the world and the highest rate of infant mortality from the disease.  We can help those patients greatly now by doing very simple things like newborn screening for sickle cell disease, immunizations,  prophylactic antibiotics and an inexpensive medication called hydroxyurea. Our department of Global Pediatric Medicine at St. Jude is working on this. Eventually, we hope that new medications and genetic therapies will become available for people with sickle cell disease who live in Africa. This will take some time. 

Q: How do St. Jude donors support the work you do?

A: When I was being recruited here, I remember (St. Jude President and CEO) Dr. (James) Downing saying to me, ‘We want you to be bold and be brave and think big.’

This cannot happen without money.   If you're going to do big things, you have to take chances. And if you take chances, you're going to fail sometimes. And you have to be brave enough to take those chances knowing that you might fail.  

Some of the money provided by generous donors to St. Jude works its way to our sickle cell program and allows us to do things that we couldn't do without it. Much of our work is grant funded, however you just can’t get enough money from grants to do the kind of work that we are now doing.  Support from the donors makes up the difference. You just can't get enough money from grants to do the kind of work that we want to do to run clinical trials. 

 For example, we are one of the very few academic centers  in the country who can run clinical trials on  genetic therapy for sickle cell disease, independent of pharmaceutical companies. I cannot thank our donors enough for providing this opportunity for our scientists, our physicians and our patients.