Sickle cell disease (SCD) refers to a group of hereditary red blood cell disorders. The disease is caused by a mutation in the DNA sequence coding for the oxygen-carrying protein, haemoglobin. This leads to haemoglobin in red blood cells becoming misshapen, resulting in the “sickle” appearance of red blood cells in SCD patients. Symptoms of SCD include anaemia, limited oxygen circulation, increased susceptibility to infections and obstruction of the blood vessels.
In rare cases, some SCD patients experience less severe symptoms due to a secondary genetic mutation in the bone marrow stem cells, where the production of foetal haemoglobin continues into adulthood. This is referred to as the “hereditary persistence of foetal haemoglobin”. Foetal haemoglobin is produced by all newborns, including those with sickle cell disease, and is later replaced with adult haemoglobin, or defunct haemoglobin in the case of those with SCD. In these patients, foetal haemoglobin production has been found to supplement defunct adult haemoglobin.
Research funded by Fulcrum Therapeutics has found a new potential treatment for SCD that takes advantage of this occurrence. In a recent presentation to the American Chemical Society, researchers presented a drug, FTX-6058, that targets bone marrow stem cells and triggers the production of healthy foetal haemoglobin cells. Initial trials on healthy adults found increased foetal haemoglobin levels constituting 25-30% of all haemoglobin in the body.
Current treatments for sickle cell disease focus on pain management and infection prevention, and stem cell transplants, the latter of which is associated with serious risks and complications. FTX-6058 was highlighted to address the root genetic cause of SCD and could be formulated into a daily tablet, overtaking current invasive treatments in terms of convenience and patient comfort. A phase 2 clinical trial involving patients of SCD is currently being formulated by the same team of researchers, with plans to launch by the end of 2021.