What is sickle cell disease?
Sickle cell disease is a type of inherited blood disorders which affects more than 20 million people worldwide. Sickle cell disease (SCD) is caused by a mutation in the amino acids which leads to a mutation in the individual’s hemoglobin. Hemoglobin is a protein that is found in red blood cells (RBCs) and helps to transport oxygen to different tissues and organs in the body. The abnormal and mutated hemoglobin caused by SCD results in the usually curved and round RBCs to turn into sickle or crescent shapes. These sickle cells have a reduced capacity to hold on to and deliver oxygen, so many organs and tissues in the body end up being oxygen deprived. The sickle cells also clog up the blood vessels and restrict blood flow which can lead to episodes of severe pain known as vaso-occlusive events (VOEs). The recurrence of these VOEs can lead to life threatening disabilities or sometimes early death.
Some already existing treatments for SCD include stem cell transplants or blood infusions, but these do not correct the underlying, genetic cause for SCD.
A new hope for patients with sickle cell disease:
On November 16, the United Kingdom (U.K.) approved a gene-editing therapy known as CRISPR-Cas9 to treat sickle cell disease. This therapy is known as Casgevy. Clinicians would administer this by taking blood-producing stem cells from the bone marrow, and use the CRISPR-Cas9 gene editing tool to target the part of the DNA in these stem cells that codes for the abnormal hemoglobin. The CRISPR-Cas9 gene editing tool uses an RNA (ribonucleic acid) molecule to locate a specific section of the DNA known as the BCL11A gene and uses an enzyme known as Cas9 to deactivate this section. The BCL11A gene is responsible for restricting the production of a type of hemoglobin that is only found in fetuses known as fetal hemoglobin. By deactivating this gene, CRISPR Cas9 boosts the production of fetal hemoglobin which is not affected by the sickle DNA mutation.
Before these genetically edited stem cells are infused back into the body, the patient undergoes a type of therapy that makes room in their bone marrow for these edited stem cells to go into. These stem cells then can produce red blood cells which carry fetal hemoglobin instead of sickle hemoglobin, and increase the supply of oxygen to the tissues.
Side effects of this therapy and cost:
Patients enrolled in this trial experienced side effects such as nausea, fatigue, fever and an increased risk of infection, but notable and major side effects were not reported.
The cost of this CRISPR Cas9 therapy for sickle cell disease, however, $2 million USD per patient, makes it unaffordable as of now for many people. The high price is likely because this is a new therapy. As more companies begin to manufacture this therapy, the higher competition would allow for the cost to decrease.
Conclusion:
I believe that CRISPR Cas9 has a great potential and provides hope for many patients who have sickle cell disease, and who until now, had no option but to live with the disease with only temporary medications. Even though CRISPR Cas9 gene editing is still a new therapy and there is yet a lot to discover of its potential, it can provide a cure for individuals living with sickle cell disease.
Sources:
https://www.nature.com/articles/d41586-023-03590-6
https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease