How Gene Therapy Could Cure Sickle Cell Anemia

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Sickle cell anemia, also called sickle cell disease, affects an estimated 100,000 people in the United States. It’s a painful disease that affects mostly African Americans. If you or someone you care about has the condition, it’s important to stay up to date on new potential treatments. One of the latest treatment advancements is sickle cell anemia gene therapy.

Sickle Cell Anemia Genetics

A lot of time and money has been dedicated to sickle cell genetics research over the past few decades. Researchers have learned that sickle cell anemia is caused by a specific mutation in the HBB gene.

The protein from the HBB gene makes up part of hemoglobin, a major component of red blood cells that carries fresh oxygen to all your body’s tissues. It also gives the cells their characteristic donut shape, which allows them to move easily through your bloodstream. However, the mutation makes an abnormal form of hemoglobin that makes it rigid and clump together. This structure causes the blood cells to be sickle shaped, which in turn causes life-threatening cardiovascular problems and significant pain.

When scientists know which gene is the problem, they have a target to work on, to improve the prognosis of sickle cell anemia. Targeted gene therapy to cure sickle cell disease (and other genetic diseases) has been attempted various ways for decades, but recent advances in sickle cell gene therapy are now making it possible to actually cure sickle cell disease.

What Is Gene Therapy?

Gene therapy is a treatment that uses your own genes and cells to eliminate diseases. Genes are composed of DNA, molecules that contain instructions for your body, such as what color your eyes are and how tall you grow. Abnormalities in your genes can also determine if you develop certain diseases, like sickle cell anemia.

As researchers get a better understanding of the role genetics play in diseases like this, they are working to find a way to use the genes to treat or even reverse the disease. With gene therapy, mutated genes could be replaced, destroyed or inactivated, or a new gene may be introduced altogether.

Sickle Cell Anemia Gene Therapy

Until recently, the only sickle cell anemia treatments included:

  • Blood transfusions to increase the number of normal red blood cells

  • Medications to manage pain during a sickle cell crisis

  • Antibiotics and vaccinations to prevent infections

  • Bone marrow transplants from others, to encourage production of normal shaped red blood cells

However, transfusions, medications, antibiotics and vaccinations don’t cure sickle cell anemia, and bone marrow transplants are not always possible. Bone marrow transplants require a donor, who has to be a close match. This can be particularly difficult in some communities. And no matter how closely matched the donor is, there is a risk of some degree of mismatch between the patient’s blood cells and the donor’s blood cells, and this conflict can cause serious complications.

Successful gene therapy as a sickle cell cure is exciting. Clinical trials are underway, looking at how gene therapy can change the course of sickle cell anemia in patients enrolled in the study. Your own blood stem cells are used with gene therapy, so there’s no need to find a match and this also eliminates the risk of conflict. 

If you were a candidate for sickle cell anemia gene therapy, your doctor would remove stem cells from your bone marrow. In a lab, scientists engineer the stem cells to make healthy forms of hemoglobin. There are various ways to change hemoglobin production. In some trials, researchers are using 'CRISPR' gene editing technology to correct the defective HBB gene. Some labs are using CRISPR or another gene editing tool to reactivate the patient's own fetal hemoglobin gene, which does not contain the mutation but turns off shortly after birth. In yet another trial, select parts of a virus are mixed with a normal copy of HBB and added to the stem cells. 

Once the engineered genes are in place, the doctor returns the stem cells to the patient via intravenous (IV) infusion. If all goes well, the gene-modified stem cells will multiply and produce normally shaped new blood cells.

Sickle Cell Gene Therapy Is Still Experimental

As promising as sickle cell anemia gene therapy may be, it’s important to keep in mind it is still experimental. Results have been good so far, with news reports featuring a few patients who are doing well. Clinical trials are ongoing, and more will come if results are good. Currently, there are trials looking at how safe and effective the gene editing is and if there are certain medications that would make collecting stem cells easier.

Sickle Cell Anemia and Umbilical Cord Blood

Saving or harvesting umbilical cord blood after a baby is born also has potential for curing sickle cell disease. Umbilical cord blood is a source of stem cells, including immature blood cells that can develop into red blood cells and all other types of blood cells. Cord blood can be donated to help anyone who needs it. It can be transplanted into someone with sickle cell anemia, with the hopes that the cord blood will grow healthy red blood cells.

Whether it’s through gene therapy or fetal blood transplantation, there is still a long road ahead in terms of finding a cure for sickle cell anemia that can be used in everyday medical practice.

A stem cell transplant not a simple procedure. Patients who undergo this type of treatment must receive strong chemotherapy to wipe out their own stem cells, which produce the sickle-shaped blood cells, while also poisoning other healthy immune cells. The patients must be kept in isolation during this time because they won’t be able to fight off infections. Once patients receive the gene-modified stem cells, it can take months for their immune system to get back to normal.

If you are interested in participating in a clinical trial, speak with your doctor. Each trial has different requirements, and not everyone with sickle cell anemia is eligible. However, there may be a trial near you that is a good fit.  

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Medical Reviewer: William C. Lloyd III, MD, FACS
Last Review Date: 2019 Jul 30
  1. Sickle cell patient’s recovery after gene therapy heightens hopes for a cure. National Heart, Lung, and Blood Institute. https://www.nhlbi.nih.gov/news/2019/sickle-cell-patients-recovery-after-gene-therapy-heightens-hopes-cure
  2. Sickle cell anemia. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/symptoms-causes/syc-20355876
  3. Sickle cell disease. Genetics Home Reference; U.S. National Library of Medicine. https://ghr.nlm.nih.gov/condition/sickle-cell-disease
  4. Data & Statistics on Sickle Cell Disease. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/sicklecell/data.html
  5. What is Sickle Cell Trait? Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/sicklecell/traits.html
  6. Advances in the Treatment of Sickle Cell Disease. Mayo Clinic Proceedings. https://www.mayoclinicproceedings.org/article/S0025-6196(18)30585-8/fulltext#sec3.4.2
  7. Why parents should save their baby’s cord blood — and give it away. Harvard Health Publishing. https://www.health.harvard.edu/blog/parents-save-babys-cord-blood-give-away-2017103112654
  8. Gene therapy in clinical trials for sickle cell anemia. Sickle Cell Anemia News.  https://sicklecellanemianews.com/gene-therapy/
  9. A Safety and Efficacy Study Evaluating CTX001 in Subjects With Severe Sickle Cell Disease. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03745287?term=crispr&cond=sickle+cell+anemia&rank=2
  10. Sickle Cell Patient Reveals Why She Is Volunteering For Landmark Gene-Editing Study. NPR. https://www.npr.org/sections/health-shots/2019/07/29/744826505/sickle-cell-patient-reveals-why-she-is-volunteering-for-landmark-gene-editing-st
  11. A CRISPR Approach to Treating Sickle Cell. National Institutes of Health. https://directorsblog.nih.gov/2019/04/02/a-crispr-approach-to-treating-sickle-cell/  
  12. Park SH, Lee CM, Dever DP, et al. Highly efficient editing of the β-globin gene in patient-derived hematopoietic stem and progenitor cells to treat sickle cell disease. Nucleic Acids Res. 2019 May 31 (epub ahead of print). https://www.ncbi.nlm.nih.gov/pubmed/31147717 


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