Long-term cures are just over the horizon for sickle cell disease in Saudi Arabia

It’s not easy living with sickle cell disease as a young adult. You’ve been in and out of hospital due to chest pain and difficulty breathing, and have probably missed a fair amount of school due to your health challenges. You’ve asked yourself many times: why is this happening to me?

Sickle cell disease is an inherited genetic condition––it comes from your parents, which you can’t help. This genetic heredity is more likely to occur in the Eastern Province of Saudi Arabia (1 case in every 69 people)[1-2], but that doesn’t mean you can’t do anything about it. Gene-editing therapy is a relatively new approach to managing sickle cell disease that is well worth investigating!

In this article, you’ll learn––in a simple way––about gene-editing therapy and a powerful tool named CRISPR, which has proven to be very effective for individuals with sickle cell disease.

What is gene editing, and how might it help you?

Sickle cell disease is caused by a genetic abnormality that makes poorly functioning red blood cells.[3] Typically, red blood cells are round, concave and contain many hemoglobin molecules that carry oxygen around your body. However, your red blood cells look and act a bit differently.

As an individual with sickle cell disease, you have a mutation in your DNA that introduces changes in hemoglobin’s structure, producing red blood cells that look like a ‘‘sickle”. These sickle-shaped cells frequently obstruct your blood vessels, which is why you experience episodes of pain.

To correct the DNA mutation that causes your pain in the first place, scientists have looked at a gene-editing approach. This technique involves altering your DNA in a way that allows it to restore the optimal shape and function of your red blood cells.

Think of your DNA as an instruction book containing four letters: A, T, G, and C. These four letters are organized in a sequential fashion to give your cells the instructions that make you who you are. With sickle cell disease, you have a mutation in your DNA sequence that reads as GTG instead of GAG.[4] It may seem trivial, but this single mutation gives your cells the wrong instructions, forming an imperfect hemoglobin structure. It is exactly like when you spell your name wrong; even a one-letter mistake can change the meaning of your name, and in fact, it’s not your name anymore!

What’s great about gene-editing is that it can remove your misplaced T and replace it with an A, fixing the root cause of your disease. Think of it as a mechanical machine combining a pair of scissors and glue work: cutting the DNA at a specific location before adding or replacing a letter within that sequence.

Now that you know the basics of gene-editing, let’s introduce you to CRISPR: a technology that scientists use to alter DNA.  

A powerful, yet simple, gene-editing tool

It’s not surprising that Emmanuelle Charpentier and Jennifer Doudna were awarded the 2020 Nobel prize in chemistry for discovering and developing CRISPR because it has revolutionized the field of genetics.[5] Jennifer Doudna, Professor of Chemistry and Molecular and Cell Biology at the University of California, Berkeley says: “we may be nearing the beginning of the end of genetic diseases.”[6]

CRISPR is unique because it has two components working together to alter your DNA. The first element is responsible for identifying the precise location of the mutation in your DNA, while the second is in charge of cutting at that exact location once determined. Your cell will then recognize that something went wrong and try to repair it.

If you’re interested in learning more about how the CRISPR system works, follow this link.

A story of hope

In July 2019, CRISPR-based therapy was used for the first time to treat Victoria Gray, who had severe sickle cell disease.[7] Gray described her sickle cell pain as lightning strikes in her chest: “It’s a deep pain. I can’t touch it or make it better; sometimes, I will be just balled up crying, not able to do anything for myself.”[8]

When the COVID-19 pandemic hit, Gray became vulnerable to developing complications, and could even die, if she caught COVID. She genuinely wanted a solution to end her pain, so she asked her doctor, Haydar Frangoul at the Sarah Cannon Research Institute, to carry out a bone marrow transplant. Instead, Dr. Frangoul invited her to enrol in a CRISPR study to treat sickle cell disease. Gray immediately felt excited and jumped at the opportunity to volunteer.[8] 

During the study, doctors removed some bone marrow cells from Gray’s body, then used CRISPR to edit the genes inside them before infusing these modified cells back into her body. After one year of CRISPR treatment, Gray has shown remarkable improvement––her hemoglobin levels increased significantly and at least 30% of her sickle cells were repaired.[7] “They go from cells that make sickle cells to super cells—the cells that help me feel better. It’s wonderful. It’s the change I’ve been waiting on my whole life,” Gray says.[7,8] You can read about Gray’s treatment journey in full here.[9]

These initial results from Gray are incredibly encouraging. “To be able to take this new technology and give people a chance for a new life is a dream come true,” says Dr.Francis Collins, director of the National Institute of Health.[8]

With all the exciting news, the FDA has approved using CRISPR therapy to correct the defect causing sickle cell disease and more clinical trials are now underway.[10] Individuals enrolled in these trials will be monitored carefully for the safety and effectiveness of the treatment before full approval from the FDA can be granted, which can take several years.[10] “We are very cautious to conduct these studies in a systematic way to monitor patients carefully for any complications related to CRISPR therapy,”[8] says Frangoul.

Where can you go from here?

While in Saudi Arabia, current treatment for pain management depends heavily on drugs like hydroxyurea and morphine.[2] But Gray’s story could spark the beginning of a new treatment option for you. If you’re interested in learning more about CRISPR therapy and how it may benefit you, speak with your family doctor and hematologist about current clinical trials. To facilitate the conversation, you may wish to refer to CRISPR clinical trials here. It’s always best to show up prepared!