Updated Blood
CRISPR-blood cured the first patients with hereditary diseases
Polina Loseva, N+1
In 2019, CRISPR Therapeutics and Vertex began the first trials of genetically edited cells to combat hereditary blood diseases. Today, the leaders of the experiments announced the first evidence of success: one of the patients who had beta-thalassemia no longer required constant blood transfusions, and the other – with sickle cell anemia – stopped suffering from vascular blockage. Next year, the companies promise to show data on CRISPR therapy for blood cancer.
Despite the fact that genetic editing technologies using CRISPR/Cas9 are actively used in basic research, they have not yet entered clinical practice. The fact is that this technique is quite young, and there is not enough data on its possible side effects yet. In addition, in many cases, the editing efficiency is quite low, and it can be difficult to gain the necessary number of corrected cells to achieve a therapeutic effect.
This summer we have already talked about the fact that the first clinical trials of CRISPR therapy aimed at combating blood diseases have been launched in the United States. Two companies – CRISPR Therapeutics and Vertex – joined forces and began searching for patients in Europe and the USA. Almost simultaneously, they took two women into the experiment – from the USA and Germany – with two different diseases: beta-thalassemia and sickle cell anemia.
These two diseases combine mutations in the hemoglobin gene, a protein that is responsible for the transport of oxygen through the blood. In the case of beta-thalassemia, blood cells cannot produce enough hemoglobin, and anemia develops, that is, a lack of red blood cells and oxygen in the tissues. With sickle cell anemia, hemoglobin takes an irregular shape, which causes red blood cells to shrink, become sickle-shaped, transport little oxygen, and also squeeze poorly through capillaries and sometimes get stuck in them.
Scientists have come up with a cure for both of these diseases in one way – they force patients' blood cells to produce not an adult, but a child (fetal) version of hemoglobin, which occurs in the body only at the beginning of life, but then disappears. To achieve this effect, scientists beat the cells with an electric current so that holes appear in their membrane, CRISPR/Cas9 molecules are injected into these holes, and those, in turn, make a cut in the DNA. With this incision, they make the BCL11A gene inoperable, which inhibits the production of fetal hemoglobin.
Patients then receive busulfan, a chemotherapeutic drug that destroys old blood cells in their red bone marrow and makes room for new arrivals. And finally, they are injected with the drug CTX001 – that is, a suspension of their own edited cells.
The CRISRP Therapeutics report reports that a patient with beta-thalassemia underwent an average of 16.5 blood transfusion procedures per year before starting treatment – exactly the amount she needed to maintain normal hemoglobin levels in the blood. After CTX001 treatment, she did not need donor blood for 9 months, and 99.8 percent of the cells in her blood produced fetal hemoglobin.
The second patient – with sickle cell anemia – suffered from vasoocclusion before therapy: defective red blood cells clogged her vessels on average 7 times a year. For four months after the start of treatment, no such crisis was recorded. 46.6 percent of the hemoglobin in her blood was related to the fetal form – while it is believed that 25-30 percent is enough to cope with the disease.
In both cases, there were also side effects, and quite severe ones – pneumonia, abdominal pain, gallstones and liver ischemia – but the study leaders considered them to be a consequence of chemotherapy, and not the action of edited cells.
The companies are going to continue CTX001 research and test their drug on 45 more people. According to the STAT portal, next year the company will present the results of CRISPR editing in patients with blood cancer.
Meanwhile, the results of the first trials of CRISPR cancer therapy have already appeared in the United States. In China, researchers have tried using CRISPR to treat HIV. In parallel, trials of other gene therapy methods are continuing: for example, sickle cell anemia was once cured with cells that were edited with the help of viral vectors.
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