Gene Therapy Has the Potential to Cure Thalassemia Patients From Their Blood Disorder

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Currently rolling out worldwide, gene therapy uses patients’ own stem cells to generate healthy red blood cells and eliminate or reduce the need for blood transfusions, says expert ahead of International Thalassemia Day

Dr. Rabi Hanna, a pediatric hematologist-oncologist

Cleveland, Ohio: sGene therapy could pave the way for patients with the inherited blood disorder thalassemia to stop or significantly reduce blood transfusions and transform their daily lives, says an expert at a top American hospital, Cleveland Clinic, ahead of International Thalassemia Day on May 8.

Dr. Rabi Hanna, a pediatric hematologist-oncologist, said: “Thalassemia is a disease that can be cured, with gene therapy as a novel step that uses the patients’ own hematopoietic stem cells to produce healthier red blood cells and fix their blood disorder. Thalassemia patients who have received gene therapy have either eliminated or significantly reduced the amount of blood transfusions needed to manage their condition. With gene therapy, we can remove the challenges that thalassemia patients face to give them the courage to pursue their goals and dreams, whether in education, careers, or families.”

Thalassemia is a blood disorder that affects the body’s ability to produce red blood cells, and hemoglobin, the protein that carries oxygen in red blood cells. Even with blood transfusion and appropriate iron chelation therapy; patients can develop iron overload, with potential to damage the liver, heart, and endocrine system.

There are two type of thalassemia, alpha and beta, depending on the defects that can occur in the protein chains that make up hemoglobin. Patients with alpha thalassemia tend to be silent carriers without symptoms, while patients with beta thalassemia major will have major symptoms early after birth and require frequent red blood transfusions. Moderate and severe thalassemia cases are usually diagnosed with early childhood blood tests. Married couples can also have genetic tests that can predict the risk of thalassemia and related blood disorders.

Worldwide, there are 270 million carriers with abnormal hemoglobin and thalassemia, with 300,000-400,000 babies born with serious hemoglobin disorders annually, according to the US National Institute of Health. It is estimated that 90 percent of those births are in low- or middle-income countries, especially in the Middle East, South and Southeast Asia, the Mediterranean, Africa, and the South Pacific. Recognizing this, International Thalassemia Day’s theme for 2021 is “Addressing Health Inequalities Across the Global Thalassemia Community.”

In contrast to time-consuming, life-long blood transfusions, gene therapy could be a one-time therapy and provide a potential cure. Despite that, the allogeneic bone marrow transplant is currently the only available option with the potential to correct the genetic deficiency in Transfusion-dependent Thalassemia (TDT), but it has possible complications such as graft failure, graft-versus-host disease (GvHD), and opportunistic infections, particularly in patients who undergo non-sibling matched allogeneic HSCT. Gene therapy, in contrast, uses the patient’s own cells and eliminates the risk of GVHD.

The challenge in Dr. Hann’s opinion is how we can make this therapy available worldwide, especially in developing countries, where most of the patients are, globally.

The European Medicines Agency has given conditional marketing authorization to one form of genetically modified products for beta-thalassemia. In the United States, there are currently clinical trials for gene therapy, and this therapy is under review by Food and Drug Administration – which experts hope could lead to authorization later in 2021.

In recent phase 1-2 studies of gene therapy for 22 patients, all of them had reduced or eliminated the need for long-term red blood cell transfusions. Of the 13 alpha-thalassemia patients, 12 stopped receiving red blood cell transfusions. For the nine beta-thalassemia patients, three stopped red blood cell transfusions, and the remaining six patients saw their median annualized transfusion volume decrease by 73 percent.

“While gene therapy is a promising cure for transfusion-dependent thalassemia, many patients do not know the whole process – including chemotherapy to get rid of the old bone marrow and create space for the new modified stem cells. This will currently require admission to hospital for four to 6 weeks until new the stem cells are working and able to produce white blood cells, platelets and healthier red blood cells,” added Dr. Hanna. “We are hopeful that in the future we can target the bone marrow more selectively using reduced intensity chemotherapy or other medication to avoid the acute and long-term toxicity associated with high doses of chemotherapy.”

About Cleveland Clinic:

Cleveland Clinic – now in its centennial year – 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 70,800 employees worldwide are more than 4,660 salaried physicians and researchers, and 18,500 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, 19 hospitals, more than 220 outpatient facilities, and locations in southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2020, there were 8.7 million total outpatient visits, 273,000 hospital admissions and observations, and 217,000 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries.