Two patients developed cancer and the trial of gene therapy for sickle cell disease was terminated
Last Update: 2021-02-23
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gene therapy has great potential for treating genetic diseases. However, Bluebird Bio, an American gene therapy company, announced on February 16th that it had suspended a clinical trial of sickle cells because of leukemia-like cancer in two patients treated. Bluebird Bio's shares plunged nearly 38 per cent on February 16th, local time.
, based in Massachusetts, USA, uses viruses to transmit therapeutic genes. The company is investigating whether the virus it used caused cancer, and the latest case has renewed concerns about the safety of gene therapy. Bluebird Bio has also stopped selling approved treatments for thalassemia using the same β blood diseases in Europe.
sickle cell anemia is an often chromosomal explicit genetic hemoglobin disease. Clinical manifestations are chronic hemolysal anemia, infection and relapted pain risk, resulting in chronic local ischemia leading to organ tissue damage. In general, patients with sickle cell anemia have a hard time living past the age of 50.
Sickle cell anemia pathogenic mechanism is that the β-peptide chain of the sixth amino acid glutamate was replaced by proline, forming sickle hemoglobin, replacing normal hemoglobin, and the most important function of normal hemoglobin is to transport oxygen. This DNA mutation increases the viscosity of β-globulin, one of the two proteins that make up hemoglobin, causing hemoglobin molecules to gather and form stiff fibers.
these stiff fibers make red blood cells that should have been in the shape of round cakes sickle-like or other deformities. Fatally, this stiff sickle cells do not pass through capillaries and increase the viscosity of the blood, blocking capillaries, activating the body's immune system, removing mutant red blood cells and eventually leading to anemia.
in a clinical trial at Bluebird Bio, patients had to undergo a series of chemotherapy treatments to prepare their bodies for gene therapy. In fact, patients may also develop cancer during chemotherapy. Donald Kohn of the University of California, Los Angeles, who led the clinical trial of gene therapy, said it was regrettable that cancer was caused by whatever the cause.
the previous clinical trial, scientists extracted the patient's hematopoietic stem cells and treated them in cultured containers with an improved HIV-related virus. It carries DNA that encodes the oxygen-carrying hemoglobin, which is designed to compensate patients for defective genes in the molecule. Because the patient's cells are genetically treated outside the body, this step is called an "off-body" test. These cells are then injected into the patient. Fourtean people have been freed from the pain caused by sickle red blood cells after receiving the latest version of Bluebird bio gene therapy.
, on February 16th, local time, it was announced that a patient who had been receiving gene therapy for five years had acute myeloid leukemia (AML). Another patient developed bone marrow growth syndrome (MDS) and may develop acute myeloid leukemia.
2018, a similar situation appeared in this clinical trial, in which a treated patient developed bone marrow growth syndrome, which tests showed may have been caused by DNA-destroying chemotherapy. The chemotherapy is designed to remove the patient's hematopoietic stem cells to make room for gene therapy-treated hematopoietic stem cells.
in previous small clinical trials, several boys with birth immunodeficiency developed leukemia after receiving gene therapy. Clinical trials at the time did this: the mouse virus with the therapeutic gene was injected into the patient, and the gene-edited mouse virus was able to transmit its genetic material to the cells, but it also opened up the cancer-causing gene. Since then, researchers have turned to a potentially safer delivery system: a lyovirus. The lysovirus can insert the genes it carries into the host's DNA, but does not trigger cancer-promoting genes. However, a 2019 report suggests that monkeys treated with lyovirus gene therapy have also developed leukemia-like diseases, suggesting that the cancer risk in gene-editing therapy has not been eliminated.
Bluebird bio has updated investors that in subjects with acute myeloid leukemia, scientists have discovered that a therapeutic virus has inserted DNA into the chromosomes of its leukemia cells, but they still don't know where it is. They will look to see if viral DNA falls near known cancer-promoting genes. The company says the tests will take weeks.
another pathway to gene therapy for sickle cell disease: using CRISPR gene editing techniques. Last year's clinical trials showed good prospects. This treatment does not rely on viruses to transmit genetic material, but rather on CRISPR technology. However, it is not clear whether CRISPR itself can produce off-target effects and rear-line chromosomes, and whether it causes cancer.
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