Researchers have taken a significant step forward in the development of new treatments for hereditary forms of anaemia. In a review article in The Lancet, Thomas Doeven, a clinician-researcher, and Eduard van Beers, a haematologist at UMC Utrecht, describe how a new class of drugs – known as pyruvate kinase activators – can restore the energy metabolism of red blood cells and thereby reduce anaemia.
Hereditary haemolytic anaemias are among the most common genetic disorders worldwide. Patients have red blood cells that break down more quickly, which can lead to chronic anaemia, fatigue, organ damage and a reduced quality of life. Current treatments are often limited to supportive care, such as blood transfusions. In severe cases, the spleen may sometimes need to be removed. Curative options, such as stem cell transplantation or gene therapy, are risky and not available to everyone.
UMC Utrecht is playing a leading role in international research focusing on a fundamental problem in red blood cells: a shortage of energy (ATP). Red blood cells are entirely dependent on glycolysis for their energy supply. When this process is disrupted, cells lose their flexibility and stability, causing them to break down more quickly. Pyruvate kinase activators stimulate this energy process and increase ATP production, enabling red blood cells to function better and survive longer.
According to Van Beers, this is a significant step forward: “By improving the energy metabolism of red blood cells, we are addressing an underlying mechanism that plays a role in several rare blood disorders.”
International clinical trials have now shown that these drugs can be effective in treating various conditions, including pyruvate kinase deficiency, thalassaemia and sickle cell disease. In these trials, haemoglobin levels increased in some patients and signs of haemolysis decreased. Patients also reported an improved quality of life.
It is expected that these therapies may become available to a wider group of patients in the future. As they address the underlying energy deficiency in red blood cells, they could be used to treat several inherited blood disorders. In doing so, they may offer a new, relatively simple treatment option for patients worldwide. For patients, this could ultimately mean that they become less dependent on blood transfusions and are better able to live with their condition.
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