Modus Therapeutics | Sickle Cell Disease

Genetic cause

The underlying mechanism for the painful crisis in this inherited blood disorder is shown in the figure below. Sickle cell disease is an inherited, or genetic, disease. There is a change in the hemoglobin-beta gene on chromosome 11 which causes defective hemoglobin. This defective hemoglobin is unable to carry oxygen as well as normal hemoglobin, and results in red blood cells that are sickled in shape. Individuals that inherit a defective gene from both parents will have sickle cell disease. Individuals with one copy of the defective gene have sickle cell trait. It is possible that people with sickle cell trait will never have any symptoms of the disease. Genetic screening has become more common with newborns often tested at birth.

Large unmet medical need

SCD is a disease with large unmet medical needs, as there is, currently, no disease-modifying treatment for an ongoing painful crisis. Patients are treated symptomatically for pain using intravenous opioids until the crisis has settled, typically within 4 – 5 days, but crises may last a week or longer. Painful crises are also treated with hydration, and in some cases, blood transfusion. For crises not requiring hospitalization or for daily pain, patients can manage on non-steroidal anti-inflammatory drugs (“NSAIDs”) and other prescription oral medications.

SCD is affecting millions of people around the globe and is caused by a mutation in the hemoglobin gene. SCD patients’ red blood cells form a sickled shape and become sticky, attaching to vessels walls and other blood cells. This leads to a reduced blood flow and impaired transport of oxygen to vital organ.

Reduced oxygen transport causes sufferers to experience acute painful crises, so called Vaso-Occlusive Crisis (VOC), and long-term organ damage over time, which leads to severe complications and early death. The severe pain is the main reason for SCD patients to seek hospital care. Current management of these painful crises is symptomatic, only treating the pain, often with strong opioids. There is currently no disease-modifying therapy targeting the blockage in the blood vessels, which would have an effect on the severity and duration of the acute painful crisis. Prophylactic therapy may reduce the frequency of crises, but this has no proven effect on the actual crisis.

SCD is an orphan disease with around 100,000 patients in the US and 40,000 in Europe. There are additionally a significant number of patients in the Middle East, India, South America and Africa. There are genetic tests available, routinely used in newborn screening programs in many countries.