For as long as it was first described in 1910, a cure for sickle cell disease had evaded experts in the medical world. All that changed this past Friday when the Food and Drug Administration (FDA) gave a nod to two revolutionary treatments for the disease. In a milestone announcement, the agency approved Casgevy and Lyfgenia as the world’s first gene editing therapies and potential cures for sickle cell disease.
In this MedDigest article, we succinctly delve into how this groundbreaking development completely reshapes how doctors approach sickle cell disease and what this means for people living with the condition.
What is Sickle Cell Disease (SCD)?
🩹Sickle cell disease (SCD) is a group of inherited red blood cell disorders.
🩹Sickle cell disease is caused by a mutation in the gene responsible for the production of oxygen-carrying hemoglobin, a protein in red blood cells.
🩹The mutation causes red blood cells to become misshapen. Under a microscope, they look like crescents or sickles, which gives the disease its name.
🩹When sickled red cells clump together, they clog blood vessels, robbing tissues of oxygen and causing bouts, or “crises,” of extreme pain, hospitalizations, organ damage, stroke, and early death.
What Causes SCD?
SCD is a genetic condition that is present at birth.
It is inherited when a child receives two genes —one from each parent— that code for the abnormal hemoglobin.
Demographics Commonly Affected
SCD affects more than 100,000 people in the United States and 20 million people worldwide, according to data from National Heart, Lung, and Blood Institute (NHLBI).
In the United States, most people who have sickle cell disease are of African ancestry or identify themselves as Black.
About 1 in 13 Black or African American babies are born with sickle cell TRAIT (HbAS), per NHLBI.
And about 1 in every 365 Black or African American babies are born with sickle cell DISEASE (HbSS).
SCD also occurs among about 1 out of every 16,300 Hispanic-American births, according to Centers for Disease Control and Prevention [CDC]).
What Are the Complications of SCD?
People with sickle cell disease (SCD) start to have signs of the disease during the first year of life, usually around 5 months of age.
Symptoms and complications of SCD are different for each person and can range from mild to severe. People with SCD can experience different complications, but some of the common ones are listed below:
- Acute chest syndrome (ACS)
A life-threatening complication in people living with SCD that can result in lung injury, breathing difficulty, and low oxygen to the rest of the body.
- Anemia
Anemia occurs due to not having enough healthy red blood cells to carry oxygen throughout the body.
- Vaso-occlusive (pain) Crisis
A severe pain crisis due to the blockade of blood vessels by sickled cells.
- Stroke
Can happen if sickled cells get stuck in a blood vessel and block blood flow to the brain.
- Priapism
Occurs when sickled red blood cells in the penis cause a persistent and often painful erection of the penis.
How is SCD Diagnosed?
SCD is diagnosed with a simple blood test called Hb Electrophoresis.
In children born in the United States, it most often is found at birth during routine newborn screening tests at the hospital.
Also, SCD can be diagnosed while the baby is in the womb.
Diagnostic tests before the baby is born, such as chorionic villus sampling and amniocentesis, can check for chromosomal or genetic abnormalities in the baby.
Talk to your doctor to find out how to get tested and to explain the results after testing.
Revolutionary FDA-Approved Therapies for SCD
Until last Friday, the only curative therapy for SCD approved by the FDA was bone marrow transplant. Marred by a myriad of complications itself, this procedure is very invasive, expensive, and risky; thus, making it limited as a definitive treatment option for people with SCD.
Considered as a landmark triumph for doctors and people with SCD (I say for humanity as a whole!), the FDA approved Casgevy and Lyfgenia as the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients 12 years and older.
A cell-based gene therapy, is approved for the treatment of sickle cell with recurrent vaso-occlusive crises (ie, pain crises).
Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology.
Patients’ blood stem cells are modified by genome editing using CRISPR/Cas9 technology.
Casgevy increases the levels of fetal hemoglobin (HbF).
In patients with sickle cell disease, increased levels of fetal hemoglobin prevent the sickling of red blood cells.
Is also a cell-based gene therapy.
Lyfgenia uses a virus (as a gene delivery vehicle) for genetic modification and is approved for the treatment of SCD with a history of pain crises.
With Lyfgenia, the patient’s blood stem cells are genetically modified to produce a type of hemoglobin that functions similarly like the normal adult hemoglobin (HbA) produced in people not affected by SCD.
Casgevy and Lyfgenia are a potential cure for SCD because the genetic fix enabled by CRISPR is designed to last a lifetime, although confirmation will require years of follow-up.
Other Therapies and Preventive Measures for SCD
- Hydroxyurea.
Is a drug that may help people with SCD ages 2 years and older by increasing the level of fetal hemoglobin.
- Vaccines.
It is important that children with SCD get all regular childhood vaccines. Adults should get flu vaccine every year as well as pneumococcal vaccine.
- Penicillin.
Greatly reduces the risk of infections in people with SCD and has been shown to be even more effective when it is started earlier.
- Blood transfusions may be used to treat severe anemia.
Bottom Line
The medical community eagerly anticipates the integration of the two new FDA-approved gene editing therapies into standard SCD treatment protocols. This breakthrough not only signifies hope for those currently affected by sickle cell disease but also sparks optimism for the broader landscape of genetic medicine.
