Gene therapy and DNA mutation repair sound like science fiction, but the future has arrived sooner than expected when two breakthrough drugs were approved for use this week to treat sickle cell anemia. What is gene therapy? How do the new drugs work? And why is this good news not only for sickle cell anemia patients? Read more about the fascinating field that has been gaining momentum in recent years, in the following article by researcher Rotem Sisso.

The US Food and Drug Administration (the FDA) recently approved two innovative drugs for the hereditary disease sickle cell anemia. The news of the approval of the drugs caused twofold excitement in the medical world: first, no effective treatment for the disease had been found to date, and medical strategy was focused on treating the complications of the disease; and second, this is the first approval of a drug that uses an innovative technology called CRISPR, developed for the benefit of the field of gene therapy and until now – only science fiction.

What is sickle cell anemia?

The role of the red blood cells in our body is to transport oxygen to the different bodily tissues on a molecule called hemoglobin. Normally, red blood cells are round and have physical properties that allow them to move freely through the blood vessels.

Sickle cell anemia is the most common genetic disease in the US, and as of 2021, there were approximately 7.7 million patients worldwide. In those suffering from the disease, a mutation in one of the genes responsible for the production of hemoglobin causes damage to the normal structure of the molecule, causing the red blood cells to lose their flexibility and creating a distorted sickle shape. The damaged blood cells may get stuck in the blood vessels and interfere with the normal flow of blood to the body’s organs, and patients may suffer from severe complications of attacks of pain, strokes, and lung damage. As noted, to date, patient treatment focused mainly on trying to relieve the pain and control complications, and the limited ability to treat the disease led many researchers to engage, in recent years, in attempts to develop new drugs.

Gene therapy - what and why?

Gene therapy is an innovative concept in the world of medicine that is based on the understanding that certain changes in human DNA can have fateful effects on the development of various diseases, such as in the case of sickle cell anemia. Gene therapy treatments attempt to address the changes that have occurred in the DNA – that is, to repair the damaged areas in the relevant genes and to cause the normal production of various components in the body – such as hemoglobin in patients with sickle cell anemia.

Gene therapy is part of a leading trend in recent years to personalize the various treatment strategies for each individual patient – we previously wrote about this in detail in the blog about personalized medicine.

The future is already here: Hope for sickle cell anemia patients

The two new drugs approved this week – Lyfgenia and Casgevy – join a short list of approved drugs in the field of gene therapy.

Lyfgenia works by introducing a vector that carries stem cells, collected from the patient in advance and engineered to contain a gene that produces normal hemoglobin (that functions in a manner similar to HbA hemoglobin in healthy adults). In clinical trials in patients with sickle cell anemia, the drug resulted in an average increase of 2.5 grams in hemoglobin and the complete prevention of blood vessel blockage events in 88% of the patients during the course of a year and a half of follow-up.

The second drug, Casgevy, works in a similar manner: the defective gene is repaired, leading to the production of large quantities of fetal hemoglobin (HbF), which enables normal red blood cell activity. In studies that examined the efficacy of the drug, it was found that 94.1% of patients with sickle cell anemia did not experience any events of blood vessel blockages in the first year after treatment.

The drug that's paving the way

The new drug Casgevy is the first drug in the world to be approved after the use of CRISPR technology – a technology that makes it possible to “cut out” damaged sections of DNA and replace them with normal sections. This is an important achievement and a significant milestone in the world of medicine, as this groundbreaking technology has the potential to help repair additional damaged genes, and is already being tested in several initial clinical trials in a variety of other diseases, such as type 1 diabetes and multiple myeloma.

The approval of the drug for sickle cell anemia will surely help many patients with the disease, and it seems that it will pave the way to help eradicate other serious genetic diseases in the near future.