When the NHLBI announced the launch of the Cure Sickle Cell Initiative on September 13, many in the sickle cell disease community responded with enthusiasm. Patients, family members, and advocates took to social media and other channels to say they are ready to do their part, starting with spreading the news about the initiative to their neighbors, communities and organizations. To help make those conversations easier, we sat down with Dr. W. Keith Hoots, director of the NHLBI Division of Blood Diseases and Resources, who answered some of the questions many still have about this milestone effort.
Hoots began by expressing hope for the 100,000 people in the United States—and the 20 million worldwide—who live with sickle cell disease, a group of inherited blood disorders. The disease is caused by a single genetic mutation that makes a person’s red blood cells form abnormal, sickle shapes, which can clog the blood vessels and deprive cells of oxygen. This lack of oxygen, in turn, can wreak havoc on the body, damaging organs, causing severe pain, and potentially leading to premature death.
“Many people with the disease really suffer,” said Hoots. “But science has advanced to a point where we think we can make a huge difference in their lives. It’s an exciting time.”
Q: So what is the Cure Sickle Cell Initiative?
A: It’s a collaborative research effort aimed at speeding up the development of genetic therapies that can actually cure sickle cell disease. Through this initiative, researchers will be taking advantage of the growing number of tools they now have to correct or compensate for the defective gene that causes this painful disease.
But here’s the key: We really want to take a focused, coordinated approach to this work, so the initiative includes not just researchers, but also the private sector, clinicians, patients, and advocacy groups—because we know that for this to be a success, everybody must be working together with all eyes on one goal. And that is to identify and support the genetic therapies we think can lead to cures—then move them into first-in-human clinical trials within the next five to ten years.
Q: Does the genetic cure already exist? Is that what the initiative is focusing on?
A: No, right now the only curative strategy for sickle cell disease is a bone marrow transplant, and that only works for the percentage of SCD patients who have a suitable donor. That’s why we need more options.
This initiative will speed up the development of several genetic technologies that have proved successful in animal models. Researchers will also be working harder on a gene transfer approach they’re currently testing in humans in a very small study. The most promising of these therapies will then be identified and moved through the review process so they can get the approval by the Food and Drug Administration (FDA). Only then we will be able to conduct the necessary clinical studies to demonstrate the safety and effectiveness of the potential cures.
Q: Is the initiative looking for a single, universal cure for sickle cell disease?
A: Ideally, we’re talking about finding cures—plural—for sickle cell disease.
From what we know about the heterogeneity of sickle cell disease and the wide age range for those who have it, there may never be just one universal cure. For instance, some of the therapies we are studying are more appropriate for older adolescents and younger adults.
The good news is that the current state of the science allows us to work on multiple emerging therapies. So through the initiative, we’ll be supporting several investigators who are using different strategies. We don’t know which one will succeed first. We don’t know which one the FDA will approve first. But the flexibility of this initiative allows us to engage patients and get their input on, and participation in future clinical trials, while also engaging investigators with different approaches, then helping them move forward.
Q: Is the initiative aimed at people in a specific age range, or are the cures for all patients with sickle cell disease?
A: Everybody with sickle cell disease matters to us, so the NHLBI will continue to work on therapies for people in all age groups.
As researchers identify promising therapies, they will follow the FDA’s established process for developing new drugs or treatments. This process usually begins with adults, who can give informed consent to accept the risks involved in any clinical trial. Once the FDA is convinced of the safety of the therapy in adults, it will consider lowering the age to include older children or adolescents. Then, if the therapy proves safe and effective for that group, it could be tested in young children.
As you would imagine, this is a cautious and deliberate step-by-step process, because safety is paramount.
Q: What about the research related to other therapies and treatments, such as bone marrow transplants? Are those part of this initiative?
A: The NIH spends approximately $100 million on sickle cell disease research each year. That investment has brought us to this point and has improved the lives of patients with sickle cell disease, and even cured some of them with bone marrow transplants. The Cure Sickle Cell Initiative adds to this progress. The therapies it will propel will add to the arsenal of tools we have to treat or cure this disease. We are continuing all of our current research, and certainly bone marrow transplant has been a cornerstone of it.