Gene-tweaked stem cells offer hope for sickle cell disease.

Gene-tweaked stem cells offer hope for sickle cell disease.

Gene Therapy Offers Hope for Sickle Cell Disease Patients

Sickle cell disease, a painful inherited condition that primarily affects Black children and adults, may have a new treatment option through gene therapy. A recent study published in the New England Journal of Medicine details a one-time, intensive process that “edits” a crucial section of DNA to alleviate symptoms.

Promising Results

The study, led by Dr. Akshay Sharma from St. Jude Children’s Research Hospital, tested the gene therapy on three severely ill young adults with sickle cell disease. The early results have been promising. The patients experienced a reduction in pain attacks and other symptoms within six to 18 months after receiving the gene therapy. Notably, one patient, who previously suffered from monthly pain attacks, had no attacks for nine months following the treatment. This improvement in quality of life is significant.

Seeking a Cure for Sickle Cell Disease

Sickle cell disease is an inherited disorder that primarily affects individuals of African, South American, or Mediterranean descent. It occurs when a person inherits two abnormal hemoglobin genes, one from each parent. Hemoglobin is responsible for carrying oxygen in red blood cells. When blood cells contain abnormal “sickle” hemoglobin, they become sticky and assume abnormal shapes. These cells can block blood flow, leading to excruciating pain “crises” and other complications such as strokes and heart disease.

While medications exist to manage sickle cell disease and alleviate pain, some patients do not respond well to drug therapies alone. Traditionally, a stem cell transplant from a compatible and healthy sibling has been the potential cure. However, finding a suitable donor is rare.

Beating the Donor Dilemma with Gene Therapy

Gene therapy offers a potential solution to the donor dilemma associated with stem cell transplants. In gene therapies for sickle cell disease, some of the patient’s bone marrow stem cells are removed and genetically modified in a laboratory. Meanwhile, the patient undergoes chemotherapy to eliminate the remaining faulty stem cells, creating space for the infusion of genetically enhanced cells. Various methods can be employed for the genetic modification, including using a virus to insert a healthy copy of the flawed hemoglobin gene or utilizing the CRISPR-Cas9 editing tool.

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The gene therapy in the study conducted by Dr. Sharma’s team employed CRISPR technology. The researchers aimed to recreate a natural phenomenon where certain individuals possess a benign genetic alteration, causing them to continue producing fetal hemoglobin instead of transitioning to adult hemoglobin. In sickle cell patients, fetal hemoglobin can serve as a substitute for the faulty adult version.

Advantages of Gene Therapy

One significant advantage of gene therapy over stem cell transplants is the elimination of the need for donors. Stem cell transplants carry risks such as rejection and graft-versus-host disease. Dr. David Williams, Chief of Hematology/Oncology at Boston Children’s Hospital, who is also studying gene therapy for sickle cell disease, highlights this advantage.

However, several important questions remain. Researchers seek to determine the extent to which gene therapies reverse sickle cell complications, how long their effects last, and whether any safety issues may arise in the post-treatment years.

Additionally, beyond the scientific evidence presented by trials, there are practical considerations. Patients may approach new medical therapies with skepticism, and gene therapy demands hospitalization for chemotherapy, making the entire process last around a year.

The Cost Dilemma

A significant concern surrounding gene therapy is the question of affordability. While the specific cost remains unknown, estimates suggest that gene therapy could range between $2 million and $3 million. The issue of cost extends to the willingness of insurance companies to cover the expenses. A recent study found that the one-time cost of gene therapy outweighed the lifetime cost of existing treatments, such as repeated blood transfusions and hospitalizations for sickle cell patients. However, if gene therapy can spare patients from these ongoing treatments, the gains in quality of life may be invaluable.

Looking Ahead

Ultimately, the recent study reveals a promising path toward a cure for sickle cell disease. The early results of gene therapy suggest its potential to significantly improve patients’ quality of life. While challenges, including cost and long-term effects, must be addressed, this groundbreaking treatment offers hope for individuals living with sickle cell disease.

References:

• Akshay Sharma, MBBS, assistant member, faculty, bone marrow transplantation and cellular therapy, St. Jude Children’s Research Hospital, Memphis, Tenn.
• David Williams, MD, chief of hematology/oncology, Boston Children’s Hospital, associate chairman, pediatric oncology, Dana-Farber Cancer Institute, Boston, and professor, pediatrics, Harvard Medical School, Boston.
• New England Journal of Medicine, Aug. 31, 2023.

For more information, visit the U.S. Centers for Disease Control and Prevention’s website on sickle cell disease.