Sickle cell disease is an inherited condition that affects red blood cells, which transport oxygen throughout the body.
The disease is caused by a mutation in the HBB gene, resulting in the production of an abnormal hemoglobin protein, called HbS.
Hemoglobin is the protein that oxygen binds to inside red blood cells. Unlike normal hemoglobin, HbS proteins stick together or polymerize, forming rigid structures inside the red blood cells, which forces these cells to adopt an abnormal and inflexible “sickle” shape and to become trapped inside small blood vessels. This results in a lack of oxygen reaching tissues, as well as inflammation and pain.
Several approved treatments can help manage the symptoms of sickle cell disease, including a few that can reverse the symptoms in some patients. Research is ongoing to find a more robust solution and to discover more effective ways of reducing disease symptoms. Experimental therapies are being investigated as well.
Currently, the only treatment that can offer a potential cure for sickle cell disease is stem cell transplantation. The procedure aims to replace the stem cells in the bone marrow — the source of new red blood cells — with healthy stem cells from a matching donor. This treatment is not available to all patients because it can be difficult to find a suitable donor.
Oxbryta (voxelotor), developed by Global Blood Therapeutics, is an approved therapy that targets the underlying cause of sickle cell disease, the abnormal hemoglobin. The therapy works by preventing hemoglobin from sticking together, which allows the red blood cells to maintain a more normal and flexible shape.
Another approved treatment for sickle cell disease is Adakveo (crizanluzumab), developed by Novartis, which contains an antibody that blocks one of the proteins in the endothelial cells of the blood vessels. This antibody prevents the protein from binding to sickle cells, thereby reducing the pain and inflammation caused by sickle cell aggregates blocking blood vessels.
Because pain is a common and debilitating symptom of sickle cell disease, clinicians may recommend painkillers such as acetaminophen or non-steroidal anti-inflammatory drugs, such as ibuprofen and diclofenac. Opioids such as codeine or morphine may also be prescribed for more severe or chronic pain. Ketamine may be used to treat acute pain caused by the disease.
Children as young as two months may be prescribed daily penicillin to prevent infections. This is called penicillin prophylaxis and should be complemented by vaccinations and antibiotics in cases of infection.
A number of new therapies are in clinical trials to evaluate their safety and effect on sickle cell disease patients.
One promising potential cure is gene therapy in which a functioning copy of the HBB gene is delivered into the patient’s body. If this gene therapy approach is successful, it should enable the patient to produce their own healthy red blood cells. Clinical trials of gene therapies for sickle cell disease are ongoing or have been completed. One example of a gene therapy to treat sickle cell disease is CTX001, by CRISPR Therapeutics.
Some experimental therapies are investigating ways to improve blood flow and reduce the number of red blood cells that get trapped inside blood vessels. These include Riociguat, Ticagrelor, Memantine, and Rivipansel.
Others are anti-inflammatories that aim to reduce pain in patients by reducing the immune response. Experimental anti-inflammatories being investigated for sickle cell disease include ACZ885 and NKTT120.
Last updated: Dec. 3, 2019
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