Combatting Sickle Cell Disease with Cell & Gene Therapy

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States, impacting approximately 100,000 Americans. The disease is caused by a gene mutation that causes individuals to produce abnormal hemoglobin, which makes it difficult for red blood cells to carry oxygen from the lungs to other parts of the body. SCD is a lifetime disease, with signs and symptoms usually appearing in infants in their first year.

Normally, red blood cells are flexible and round, allowing them to move easily through the blood vessels. But in SCD, the red blood cells are shaped like crescent moons or “sickles.” The irregularly shaped blood cells become rigid and sticky and can get stuck in the small blood vessels, causing slow or blocked blood flow and reduced oxygen levels, all of which can to organ and tissue damage and episodes of pain crisis.

For many, these pain crises are severe and may happen several times a year and require hospitalization. SCD also leads to anemia due to a shortage of healthy red blood cells, chronic pain, frequent infections and delayed growth and vision problems. Moreover, SCD is life-threatening, due to potential complications from blocked blood vessels, which can include stroke, difficulty breathing, pulmonary hypertension and other organ damage.

Along with the tremendous clinical burden associated with sickle cell disease is substantial economic burden. Pain crises are the source of significant health care utilization and the most common cause of ER visits and hospital admissions among SCD patients. Total direct medical costs associated with SCD are estimated to exceed $1 billion annually. Additionally, SCD patients are estimated to lose $750,000 in lost income over a lifetime due to missed workdays, loss of employment and premature mortality. In the workplace, 85% of SCD patients report pain as the most common reason for loss of productivity.

While total life expectancy for people with SCD was only 14 years in the early 1970s, today average life expectancy is 54 years, due to improved screening and therapeutics. Treatments available today can help reduce anemia and pain crisis and associated hospitalizations. At present, a blood and bone marrow transplant are the only cure for SCD, but most patients are ineligible as many are unable to undergo the transplant due to age or lack of a well-matched genetic donor. Additionally, more than 75% of adults with the disease and frequent pain crises do not receive the recommended treatment.

Sickle cell disease disproportionately impacts people of African ancestry or people who identify themselves as Black, occurring in roughly 1 in 365 Black births. But nearly every ethnic population is affected, including those of Hispanic, Indian, southern European and Middle Eastern descent.

Scientists have long observed that individuals who are carriers for SCD (with one sickle gene and one normal hemoglobin gene) demonstrate protective advantages against malaria. As a result, sickle cell carriers are highly prevalent in populations from areas of the world were malaria is very frequent, with sometimes 10-40% of the population carrying this mutation.

America’s biopharmaceutical companies are researching and developing new treatments to alleviate the tremendous burden of this devastating and painful disease and to improve the quality of life for sickle cell patients. A 2019 report found there are nearly 20 medicines in development for sickle cell disease, including multiple cell and gene therapies. These cutting-edge therapies offer the potential for a one-time treatment or cure for SCD by addressing the underlying genetic cause of the disease and helping the body to produce healthy red blood cells. A few notable examples include:

• An investigational potential one-time gene therapy that uses stem cells from the patient and inserts a corrected gene using a lentivirus, before returning the cells to the patient
   
• A gene-edited cell therapy that could potentially be a one-time treatment for SCD by using zinc finger nucleases (ZFNs), which consists of a protein with a DNA-cutting enzyme, to modify a patient’s own hematopoietic stem cells to produce normal-shaped red blood cells containing increased fetal hemoglobin
   
• An ex vivo gene-edited cell therapy that uses a new technology called CRISPR (clustered regularly interspaced short palindromic repeats) to replace stem cells with those engineered to produce high levels of fetal hemoglobin in red blood cells, replacing the damaged hemoglobin

While treatments are in development, none can happen without volunteers to participate in clinical trials. It’s crucial that health care professionals discuss the importance of participation in clinical trials with their SCD patients and patients visit ClinicialTrials.gov to find a trial for consideration.

Research and development of new treatments for SCD holds incredible promise, and as we continue to work together to develop a health care system that can ensure timely and equitable patient access, it’s critical we protect the American R&D ecosystem that continues to foster the development of these and other revolutionary treatments.

Learn more about recent advancements to help treat sickle cell disease.