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FAQ: We cured sickle cell disease???
Breaking down scientific breakthroughs with FAQs
Welcome to the first installment of FAQ, where we take a closer look at some of the key terms and concepts related to today’s scientific breakthrough. Today’s breakthrough: a cure for sickle cell disease!
So what happened earlier this month?
The FDA, the American regulatory agency in charge of deciding what medications can be sold on the market, approved the first CRISPR-based gene therapy to treat sickle cell disease, Cagevy (Source).
Why is this a big deal?
Sickle cell disease, which affects about 100,000 Americans (Source), is a gnarly condition to have, and before last week, sickle cell patients’ standard (and only) option meant a lot of pain and a lot of hospital visits (Source).
Sickle cell patients have a genetic mutation in the protein hemoglobin, a protein in red blood cells used to transport oxygen throughout their body. This mutation makes their red blood cells, which are circular in healthy humans, a sickle shape.
Day-to-day, patients report extreme tiredness, frequent occurrences of pain crises, and difficulty moving specific parts of their body due to the lower efficiency of their red blood cells' oxygen-transportation capabilities.
Before last week, the only effective treatment that could address the underlying disease was a bone marrow transplant. Bone marrow produces red blood cells, and by replacing the bone marrow of a sickle cell patient with that of a healthy donor, the sickle cell patient’s body “learns” to produce red blood cells in the right shape (Source).
Bone marrow transplants are difficult to execute in practice because finding a compatible donor is extremely challenging. A compatible bone marrow donor must have the same “cellular ID” or genetic fingerprint on the surface of their cells as the patient. Like fingerprints, there is significant variability in “cellular IDs” among humans (Source, Source).
For a patient not to reject a bone marrow transplant, the proteins of the surface of the bone marrow transplant, the “cellular ID”, need to match the “cellular ID” of the patient’s cells. Genetically related familiy, particularly siblings, are most likely to have sufficiently similar “cellular IDs”, although even genetic relation is not a guarantee of compatibility (Source).
How is this medication different from other medications?
Aside from bone marrow transplants, the only medications available to treat sickle cell disease before last week were symptom-focused, meaning that they had no impact on the underlying disease (Source).
The new medication, Casgevy, approved last week essentially allows sickle cell patients' cells to un-learn how to make sickle-shaped, unhealthy blood cells and re-learn how to make round, healthy blood cells (Source).
To accomplish this, patients’ bone marrow cells are taken into the lab, where the genetic code, basically the recipe, for making red blood cells, is replaced. The technology used to accomplish this recipe-replacement is CRISPR (Source). These enzymes, originally derived from bacteria, allow scientists to delete and replace key genetic codes, allowing the cells to make proteins using a different recipe (Source).
After sickle cell patients receive the new bone marrow cells, they are effectively cured of their disease because their new bone marrow cells are producing healthy, correctly shaped cells. This means no more pain, no more fatigue, and no more hospital visits (Source, Source). How long the cure will last remains to be seen, because the technology is so new. Patients may require re-treatment every few decades if this cure “wears off” (Source).
Can this work in other diseases?
Yes, although we need more studies!
In addition to sickle cell, CRISPR therapeutic technologies can essentially cure hundreds of diseases caused by known genetic mutations (Source). CRISPR is a revolutionary and life-saving tool in our medication arsenal, which would allow us to tackle the underlying cause of debilitating genetic diseases at the source (Source).
Ok, so how does this relate to gene and cell therapies?
CRISPR is one of multiple new and exciting gene and cell therapeutic technologies at the forefront of pharmaceutical development (further reading here).
The term “gene and cell therapy” refers to a group of technologies that change the genetic code of patient to address, and often cure, their disease. While Casgevy is a CRISPR-based ex-vivo (outside of the body) cell therapy, other gene and cell therapies use different tools to copy/paste genetic changes. These include viral vectors and DNA therapies (Source, Source).
While there are multiple viral vector and DNA therapies on the market today (Source), Casgevy is the first CRISPR-based therapy to enter the US and EU markets (Source, Source) and will likely expand to other countries soon.
Despite entering the US and EU markets, Casggevy will likely face substantial reimbursement hurdles in the coming years, given its multi-million dollar price point (Source). For Casgevy to be widely accessible, insurance companies around the world and the manufacturer will need to agree on a price point.
What other gene and cell therapies can I expect to see in the news in the next year?
Multiple gene and cell therapies are currently being studied, and we will likely see a new development in this space almost every day next year. I’m particularly excited about gene therapies to treat other genetic disorders, such as Hemophilia B (Source). However, given that the technology is still relatively new, additional innovation is needed to unlock the true therapeutic potential of these technologies at scale (Source).
