Cleveland Clinic is leading clinical trials on gene therapy as a potential cure, while new medications are already improving quality of life for people with the inherited blood disorder
CLEVELAND: While the world marks UN-designated World Sickle Cell Day on 19 June, global health system Cleveland Clinic is making great strides in a clinical trial to evaluate the use of gene-editing therapy as a potential cure for the disease. According to the lead investigator of the clinical trial, this is one of several significant recent developments that can benefit patients with the inherited blood disorder.
Rabi Hanna, M.D., a pediatric hematologist-oncologist at Cleveland Clinic Children’s, says, “This is an exciting time in the field of sickle cell disease, with the advances in research and development of new therapies offering real hope to patients. Sickle cell disease can severely impact on patients’ quality of life and limit their potential due to the extreme pain episodes, end-organ damage, and reduced life expectancy. Medications can modify disease severity and treat symptoms, but the average life of a sickle cell patient is in the mid-40s, which is why it is important for us to find a cure.”
In people with the disease, a genetic change in DNA causes a chemical alteration in hemoglobin — a red protein responsible for transporting oxygen in the blood — resulting in cells becoming sickle shaped, rather than round. The sickle-shaped cells do not pass easily through blood vessels, and can clog or break apart, leading to decreased red blood cell life and increased iron storage in the liver and heart. This can cause conditions such as liver fibrosis, liver failure, stroke, cardiomyopathy and heart failure along with severe pain.
Dr. Hanna explains that although sickle cell disease was discovered as early as 1910, there was little research or progress in its treatment until recent decades. From the 1990s onwards, a blood or marrow transplant began to be offered as a cure for select sickle cell disease patients, but it could be challenging to find a matched donor and there were significant risks involved. In the past 10 years, the potential donor pool for patients has been expanded due to new procedures for haplo-identical transplants pioneered by centers such as Cleveland Clinic, but the significant risks remain a problem.
Explaining the risks, Dr. Hanna says, “First, there is a 5% to 10% risk of your body rejecting the donor cells. Second, there is the risk of severe graft-versus-host disease, which occurs when donor bone marrow or stem cells attack the recipient. To prevent this, the patient is given strong immunosuppressant drugs, but there is still a significant risk of graft-versus-host disease.”
In contrast, gene therapy uses the patient’s own stem cells and, therefore, the risks of rejection or graft-versus-host disease are eliminated, Dr. Hanna explains. Another benefit of gene therapy is that patients will not need immunosuppressant drugs so their immune systems will function normally, which is particularly important during a pandemic, he says. In addition, while patients need chemotherapy to prepare the body in both traditional transplants and gene therapy, the chemotherapy used in gene therapy is less strong.
Describing the procedure, Dr. Hanna says, “Gene therapy is a ground-breaking technology that works by replacing or inactivating disease-causing genes. In our clinical trial, we are introducing healthy genes into the body with the goal of correcting genetic abnormalities of red blood cells. By enabling the cells to produce more fetal hemoglobin, this treatment has the potential to cure sickle cell disease in a precise way.”
During the study, patients’ stem cells are collected for gene editing in a laboratory. Patients are then treated with chemotherapy to destroy the remaining bone marrow to make room for the repaired cells that are infused back into the body. The patients will undergo the treatment at different times and will be monitored closely afterwards for up to two years to see if there are any long-term side effects before the trial results are released.
In the meantime, however, patients living with sickle cell disease are benefiting from other recent research that has led to the introduction of newer medications for the first time after many years, says Dr. Hanna. The medications, which were approved by the US Food and Drug Administration (FDA) in 2019 and 2021 respectively, are crizanlizumab to reduce severe pain and complications, and voxelotor to help restore normal red blood cell function and oxygen delivery to tissues and which also helps with pain.
“For patients and the medical community, there is a lot to be optimistic about on this year’s World Sickle Cell Day. After little progress in treatment methods during the last century, the disease is now being given the attention it deserves and all of the current research projects underway are set to make a real difference in patients’ lives,’ concludes Dr. Hanna.
According to the World Health Organization, approximately 5% of the world’s population carries trait genes for hemoglobin disorders, mainly, sickle-cell disease and thalassemia. It should be noted, however, that this does not mean they will develop the disease. It is estimated that 300,000 babies with severe hemoglobin disorders are born each year. India and countries in the Middle East and Africa are among those with a higher prevalence for sickle cell disease.
About Cleveland Clinic Children’s
Cleveland Clinic Children’s is a part of the Cleveland Clinic health system and offers full medical, surgical and rehabilitative care for infants, children and adolescents. Cleveland Clinic Children’s supports 389 beds in four acute care hospitals and one post-acute specialty hospital. In addition, pediatric services are available at more than 50 outpatient clinic locations across Northeast Ohio. A staff of more than 300 full-time pediatricians and sub-specialists see 750,000 pediatric visits each year and provide hospital care for 13,000 children per year. Cleveland Clinic Children’s is a non-profit, multi-specialty academic medical center integrating clinical care, research, and education. Cleveland Clinic Children’s consistently ranks among the “Best Children’s Hospitals” by U.S. News & World Report.
About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 72,500 employees worldwide are more than 5,050 salaried physicians and researchers, and 17,800 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,500-bed health system that includes a 173-acre main campus near downtown Cleveland, 22 hospitals, more than 220 outpatient facilities, including locations in northeast Ohio; southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2021, there were 10.2 million total outpatient visits, 304,000 hospital admissions and observations, and 259,000 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries.
