(Anthem Pictures / Sarah Cannon Research Institute via AP, File)
Gene Therapy Offers Potential Cure for Sickle Cell Disease
Sickle cell disease is a debilitating and painful inherited blood disorder that predominantly affects Black people in the United States. The only known cure for this condition, until now, has been a bone marrow transplant, a complex procedure requiring a closely matched donor without the disease and carrying risks of rejection. However, a groundbreaking gene therapy, based on CRISPR technology, has the potential to change the landscape of sickle cell disease treatment. In this blog post, we’ll explore the latest developments and the hope that gene therapy brings to those suffering from this painful and life-altering condition.
The Promise of Gene Therapy:
On Tuesday, advisers to the Food and Drug Administration (FDA) began reviewing a gene therapy for sickle cell disease, which is characterized by a genetic mutation that causes red blood cells to take on a crescent shape, leading to blockages in blood flow, severe pain, organ damage, and various other complications. This gene therapy, called “exa-cel,” represents a novel approach to treating sickle cell disease at its genetic source.
If approved by the FDA, exa-cel will mark a significant milestone as the first gene therapy on the U.S. market based on CRISPR, the revolutionary gene editing tool that earned its creators the Nobel Prize in 2020.
How Gene Therapy Works:
The exa-cel gene therapy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics, doesn’t require a bone marrow donor. Instead, it involves a one-time, permanent alteration of the patient’s DNA in their blood cells. The goal is to prompt the body to produce fetal hemoglobin, a form of hemoglobin present at birth but replaced by a defective adult form in individuals with sickle cell disease.
In the treatment process, stem cells are extracted from the patient’s blood, and CRISPR technology is used to disable the gene responsible for the switch to the adult form of hemoglobin. Medications are then administered to eliminate other flawed blood-producing cells, and the patient’s own modified stem cells are returned to their body.
Promising Results:
Though the treatment has been tested on a relatively small number of patients, early results are highly encouraging. In a pivotal study, 29 out of 30 patients who had at least 18 months of follow-up were free of pain crises for at least a year, and all 30 avoided hospitalization for pain crises during that time. Patients like Victoria Gray, the first to undergo this gene therapy, have described transformative improvements in their quality of life, including the ability to run around with their children and work full-time jobs, free from the fear of debilitating pain.
Addressing Safety Concerns:
While the potential of exa-cel is groundbreaking, the FDA is taking precautions by seeking expert advice on the possibility of “off-target effects.” These are unexpected and unwanted changes in a person’s genome that may occur during CRISPR-based treatments. The FDA wants to ensure that the risk assessment for such effects is comprehensive. If approved, the company plans to conduct post-approval safety studies and provide clear product labeling outlining potential risks.
A Second Contender:
In addition to exa-cel, another gene therapy for sickle cell disease, developed by Bluebird Bio, is awaiting FDA approval. This therapy aims to introduce functional copies of a modified gene that encourages the production of “anti-sickling” hemoglobin, potentially reversing or preventing the formation of misshapen cells.
Considerations of Cost:
While the potential price of these gene therapies has not been disclosed, a recent report suggests that costs of up to approximately $2 million for these treatments would be cost-effective in the long run when compared to the lifelong medical expenses associated with current sickle cell treatments.
Conclusion:
The prospect of gene therapy for sickle cell disease is a ray of hope for those who have long suffered from its debilitating symptoms. The FDA’s review of these groundbreaking treatments marks a significant step toward a future where this inherited blood disorder may no longer dictate the lives of those affected. While there are considerations and precautions to address, the potential for a cure is an exciting development that could offer relief and an improved quality of life to thousands of individuals living with this condition.
