For the first time in the world, the use of CRISPR gene editing technology in the treatment of diseases has been allowed. The first technology to receive this permission was Exa-cel, known as Casgevy.
The authorization, granted by the UK Medicines and Healthcare products Regulatory Agency (MHRA) on November 16, will be used in the treatment of sickle cell anemia and transfusion-dependent Mediterranean anemia. Previously, the US Food and Drug Administration had declared that the drug was safe for clinical use, but did not allow it to be used in treatments. These permits were expected to be approved in December 2023.
A new era may begin in gene therapy
The MHRA’s decision is historic. Following this decision, gene therapy will become a much more popular and accepted method and can be used to combat many hereditary diseases. However, the decision raises many questions that need to be answered regarding sustainability, cost and long-term impacts.
Casgevy will first be used to treat sickle cell anemia and transfusion-dependent Mediterranean anemia. In the first of these diseases, red blood cells are not round but have a sickle-like structure. These cells have problems such as getting stuck on each other and blocking the vessels, causing pain and a feeling of pain, and short lifespan. If care is not taken, this disease can cause serious consequences.
In Mediterranean anemia, the number of red cells in the blood is very low. In transfusion-dependent Mediterranean anemia, this production is so low that patients must have regular red cell transfusions to survive. Gene editing seems to be an important alternative for the treatment of these genetically occurring diseases.
How does CRISPR work?
CRISPR technology, which first appeared in 2012, actually has a very simple working logic. In essence, CRISPR is used as ultra-precise genetic scissors. An RNA suitable for the part of the DNA that needs to be changed is synthesized and combined with an enzyme called Cas9. The part containing the faulty code from the double-stranded DNA is cut out and the edited version is added instead. In other words, if we consider people as digital products, some of the codes in our source software can be cleared of errors in this way.
Casgevy also targets a gene called BCL11A. This gene synthesizes a protein that, under normal conditions, enables the transition of hemoglobin from the fetal version to the adult version. However, adult homoglobins are problematic in sickle cell anemia and Mediterranean anemia. With the discontinuation of BCL11A, hemoglobins can continue to be used as they were at birth.
On the other hand, this process will not be easy at all. People may need to be hospitalized for about 1 month for all hemoglobin levels to gradually change and red cell formation in the bones to reach the desired level. Additionally, the drug will be taken together with some immunosuppressants.
Yet 28 of 29 sickle cell anemia patients who participated in clinical testing did not experience an episode of pain for more than a year. 39 of 42 Mediterranean anemia patients did not need red cell supplementation during the same period. The need for blood supplements in the remaining three patients was reduced by 70%.
Genetic editing raises safety concerns.
In the eyes of many, genetic editing is an important weapon in the fight against disease. However, there are some general concerns about this issue. David Rueda, Head of the Department of Molecular and Cellular Biophysics at Imperial College London, said: “CRISPR is known to have unknown consequences on cells receiving treatment. It may be essential to see sequencing data for the entire gene to reach a conclusion.” He uses the expressions. This makes it necessary to examine all DNA for unexpected effects of CRISPR treatment.
It is not yet known when Casgevy will be available to patients. The ability to use the treatment depends largely on knowing its costs. Let’s say that gene therapy can cost millions of dollars. Vertex, which developed the drug, has not yet announced a price, but the company continues to negotiate with the authorities to ensure that the drug reaches patients and is covered by insurance.
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