Sickle cell anemia: Genetic scissors drug approved for first time

Last Updated on December 9, 2023 by Joseph Gut – thasso

November 25, 2023 – Sickle cell anemia  is an inherited disease of red blood cells (erythrocytes). It belongs to the group of hemoglobinopathies (hemoglobin disorders) and leads to corpuscular hemolytic anemia. Affected people have a mutation in the hemoglobin β chain. Either all β chains can be affected (severe form, homozygous), or only part (milder form, heterozygous). The disease occurs mainly in people from Africa and their descendants, but also in parts of the Mediterranean and the Middle East.  in India and spread globally through migration. It is still associated with high mortality in developing countries.

In the UK, a drug based on CRISPR/Cas genetic scissor technology has been approved for the first time in the world, according to the MHRA (Medicines and Healthcare products Regulatory Agency). Casgevy (exagamglogene autotemcel) is the name of this drug approved for the treatment of two genetic blood disorders, namely sickle cell anemia and beta thalassemia in patients aged twelve years and above. The hope is that Casgevy will work for the long term, perhaps for a lifetime.

Both genetic blood diseases are caused by errors in the hemoglobin gene. Hemoglobin is found in red blood cells and is used to carry oxygen. The so-called CRISPER/Cas genetic scissors can be specifically aimed at repairing individual faulty genes.

Casgevy is used to modify faulty genes in patients’ bone marrow stem cells so that they can produce functional hemoglobin, according to the MHRA. To do this, stem cells are taken from the bone marrow, processed in the laboratory and then reinserted into the patient. A hospital stay of several weeks is necessary for therapy. In a recent

clinical trial, of 28 sickle cell patients treated with this drug, 97 percent did not suffer from severe pain attacks for at least a year. In the clinical study of patients with beta thalassemia requiring blood transfusions, 93 percent (39 of 42 patients) did not require a red blood cell transfusion for at least twelve months. In the remaining three patients, a reduction of at least 70 percent in blood transfusions was possible. However, the treatment has the potential to last a lifetime, which represents a huge advancement in the treatment of these diseases, because on the one hand, sickle cell disease and beta thalassemia are painful, lifelong diseases that can be fatal. in some cases and, on the other hand, a bone marrow transplant was until now necessary, which had to come from a compatible donor and carried a risk of rejection, was the only permanent treatment option.

However, the therapy also raises some concerns. Clinical researchers at the University Hospital Regensburg emphasize that we cannot be 100% sure that the genetic scissors will not also modify other sections of DNA. Additionally, CRISPER therapy carries significant side effects and the therapy is extremely expensive and therefore likely not accessible to all potential patients due to lack of necessary resources.

Additionally, the therapy is extremely complex, requires complex logistics and is unlikely to be infinitely scalable due to the resources required, but will only be available to a limited number of patients per year. Current clinical trials of the therapy are promising, but even patients initially treated have only been followed for about four years. Although there is no evidence of this yet, it could be that the effect of gene therapy diminishes over the years, for example because the lifespan of the manipulated blood stem cells is shortened.

The drug is manufactured in a collaboration between Vertex and CRISPR Therapeutics, headquartered in the United States and Switzerland. The two companies estimate that around 2,000 people in the UK are currently eligible for Casgevy treatment. CRISPER is already used in various fields of medicine and even in plant biology (see thasso here and here, for example). The American Food and Drug Administration (FDA)  considers the approval of a first CRISPR gene editing treatment that may cure sickle cell as well.

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