Genetic Therapies Offer Hope for Sickle Cell Disease Relief.

Sickle cell anemia or sickle cell disease (SCD) isn’t a single condition. It’s a group of blood disorders that share a common tendency for the blood cells to assume a banana or sickle shape in low-oxygen areas of the body. The disease is inherited in your DNA from traits passed on by your parents. 

Sickle red blood cells are firm and less flexible than normal disc-shaped red cells. These cells don’t flow through arteries and veins well and can block blood flow, causing occlusion (obstruction) of the blood vessels, which is a central feature of the disease. 

This can cause serious problems including acute pain episodes, chronic pain, lung complications, stroke, kidney and liver disease, priapism in men, and skin ulcers. The risk of lung and kidney infections (i.e. pneumonia and UTIs) is increased. Hemolysis or early destruction of the abnormal sickle red cells leads to a shortened life-span of the cells and severe anemia. The ability of the red cells in the sickle cell diseases to carry oxygen to organs is compromised.

New genetic therapies were approved late last year for SCD and the numerous clinical trials underway give my colleagues and patients with SCD at MedStar Georgetown Cancer Institute reason to have hope. 

SCD symptoms and diagnosis.

In the U.S., approximately 100,000 people have SCD. More than 90% of patients are Black or African American, and 3-9% are of Hispanic descent. Many people with SCD report challenges accessing care and feel stigmatized with their symptoms being dismissed by health care providers. 

People with sickle cell disease live an average of 20 years less than unaffected individuals. Symptoms usually appear at about five months of age and may include:
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• Dactylitis—painful swelling of the hands and feet
• Extreme tiredness or fussiness
• Yellow color of the skin and eyes (jaundice)

Pain is a classic SCD symptom. An acute pain crisis causes intense, stabbing pain that can require hospitalization. Flare ups can happen without warning, as cell that are sickling block blood flow and cause bone infarction (death of bone tissue) and deprivation of oxygen to tissues. Triggers can include dehydration, high altitudes, illness, stress, or changes in temperature. Pain medication, massage, yoga, and guided meditation can relieve symptoms.

For about 55% of adult patients, SCD causes ongoing, chronic pain. This pain is present on most days of the week, and can have multiple causes, including damage to the joints or spine.  Chronic pain does not respond well to opioid medication. Patients with SCD can experience both chronic pain and acute episodes.

SCD symptoms and organ complications include:

• Acute chest syndrome, a life-threatening complication that requires immediate medical care
• Blood clots
• Delayed growth
• Enlarged or involuted spleen
• Eye damage (retinopathy)
• Gallstones
• Heart -failure
• Infection
• Avascular necrosis of the joints (loss of blood supply to bone)
• Kidney problems
• Leg ulcers
• Liver disease (hepatopathy)  
• Long-term pain
• Painful erections (priapism)
• Pregnancy complications
• Vitamin deficiencies (B12, B6) 
• Stroke and silent brain injury 
• Neurocognitive deficits

Complications from SCD can be life threatening. It is important to seek medical care if you experience symptoms such as severe pain, cough, chest pain, shortness of breath, and/or fever of greater than 101.3 degrees Fahrenheit, priapism, or stroke symptoms (weakness on one side, slurred or loss of speech, headaches).

Doctors can diagnose SCD through blood testing or genetic testing. Healthcare providers can test a sample of amniotic fluid or placenta to learn whether a fetus has SCD before a baby is born. 

They can also test the blood of a newborn to learn if the baby has SCD or carries it in their genes. About 1 in 13 Black babies is born with sickle cell trait, and while they don’t have symptoms, it is important to test for sickle and other hemoglobin traits in pregnancy  

Related reading: Bloodless Medicine and Surgery: An evidence-based, collaborative, multi-disciplinary approach developed to treat Jehovah’s Witnesses.

Managing sickle cell disease.

Medications, blood transfusions, and pain medications can help control SCD symptoms and reduce the likelihood of complications. Some patients benefit from a blood transfusion, in which red blood cells from donated blood are transferred to the body, replacing sickled cells with more flexible cells.

A child with SCD may be a candidate for a bone marrow transplant, which is a procedure used to replace the bone marrow of the host with sickle cell disease with stem cell from a healthy donor who does not have sickle cell disease. With a carefully matched donor, blood and bone marrow transplants successfully cure SCD about 85% of the time.

Gene therapies approved for sickle cell disease.

December 8, 2023, was a memorable day for patients with sickle cell disease and doctors like me who work to help them. That was the day the U.S. Food and Drug Administration approved two genetic therapies to treat SCD.

Both one-time treatments alter the patient’s stem cells in a lab. Stem cells are removed from the patient’s blood and altered in the lab to silence the sickle cell gene.  

Casgevy uses the gene editing tool CRISPR to “turn off” a gene in red blood cells to allow the body to produce of fetal hemoglobin. Lyfgenia adds genetic material to stem cells to enable production of adult hemoglobin that resists sickling. 

After the editing process, the stem cells are then transplanted back into the patient through an IV to make a new blood cell system. Doctors carefully monitor patients for side effects during a three- to six-week stay in the hospital.

My colleagues and I are excited about the potential benefits of these therapies and are working through the details of offering these curative treatments at MedStar Health.

Related reading: Sickle Cell Disease: Know the Facts

A time for hope and working together to change SCD.

Patients with sickle cell disease face significant barriers, including social isolation and systemic inequities that lead to disparities in care. Too few providers choose to specialize in this condition, and too little funding is committed to research. 

Yet despite all these challenges, now is a time for hope. Organizations such as the Maryland Sickle Cell Disease Association and the Sickle Cell Disease Association of America are doing important work in education, advocacy, and support for patients and families. Genetic therapies offer new reason for optimism, and we’re learning more about how to help every day. 

I speak often with my patients about the benefits of participating in research, yet many studies are stopped early because too few – patients sign up. I tell my patients, that participation in research has the advantage of giving them access to new treatments early.  Further, you’ll be helping - the effort to bring to the clinic better treatments for SCD that can prevent pain and organ damage due to sickling.  

In our hospital, we are currently participating in three clinical trials. Our participants are helping to grow our understanding of sickle cell disease—the more we know, the better we can help patients today and tomorrow lead longer, healthier lives.