Sickle cell disease is one of the most prevalent genetic diseases in the European Union,

which leads to a reduced life expectancy and a potential risk of developing complications. This type of anaemia is characterized by unusually sickle-shaped red blood cells that change the rheological properties of blood. These changes can lead to disturbances of blood circulation, severe anaemia, lung diseases, silent brain injury, and a significant risk of developing cardiovascular diseases. Sickle cell disease affects haemoglobin – the protein that carries oxygen through the body inside red blood cells. Symptoms and complications include haemolytic anaemia, and vascular occlusion, which lead to painful episodes, neuro-cognitive deficits, and organ failures. Depending on the mutation, there are several types of sickle cell disease: SS – referred to as sickle cell anaemia, most common and severe; SC – the second most common but less severe; Sβ+ thalassemia, which is milder and severe, and Sβ0 thalassemia which has a poor prognosis. The disease has an autosomal recessive inheritance pattern, and symptoms are developed when the patient inherits two abnormal haemoglobin genes, one from each parent.

CRISPR-related gene editing enables researchers to edit parts of the genome by removing, adding, or altering sections of the DNA sequence. Errors in genetic code are decoded in the wrong RNA, which leads to the synthesis of mutated proteins in the cell. This approach ensures that small guides RNA are delivered to a target location in the genome, where they serve as a “molecular scissors protein” which removes the mutated DNA sequences. In this manner, the incorrect gene can be either turned off or fixed with the correct DNA code.

Gene therapy will provide a significant therapeutical potential to treat sickle cell disease, which negatively impacts patients’ quality of life and leads to productivity loss. Multiple clinical trials are studying the therapeutical efficacy of this novel approach. Current treatments aim to reduce symptoms, improve quality of life, and prolong life expectancy. They consist of complex therapy, which is often associated with transfusions and bone marrow transplantation. Sickle cell disease requires lifelong treatment, which results in high expenditure on healthcare and public resources. The financial aspect of sickle cell disease therapy is a leading challenge for the healthcare system.

Sickle cell disease: What potential breakthrough are we awaiting?

CRISPR-related gene therapy will improve the life expectancy and productivity of patients. This therapeutic approach will alleviate the pain and psychological distress. This therapy will provide numerous socio-economic benefits as it will improve the productivity and autonomy of patients. In this manner, the quality of life of patients will be improved, and the expenditure on healthcare resources will be reduced. CRISPR-related gene editing will restore blood cells to their normal shape following a single administration. In this manner, the risk of complications will be eliminated for at least three years in some patients.

How will this approach help the patients?

How many patients will be concerned?

The number of patients with sickle cell disease in the European Union exceeds 52 thousand. The disease is characterized by acute symptoms and deterioration of the quality of life, productivity, and autonomy of patients. CRISPR-related gene therapy will offer the possibility to engage in professional life because it will alleviate the symptoms and reduce the risk of long-term complications. Providing an effective therapeutic potential following a single dose administration will prolong life expectancy and improve productivity. In this manner, patients’ dependency on healthcare will be reduced, as well as the emotional burden on relatives. Preventing complications will enhance the quality of life and offer possibilities to participate in activities of daily living. The innovative CRISPR-based therapy will alleviate the symptoms and replace the lifelong treatment. Mild and severe sickle cell disease leads to painful episodes and requires transfusions, which is significantly burdening the healthcare system. Reduction in hospitalization and dependency on healthcare will contribute to the better financial and economic productivity of patients.

What will be the potential impact on healthcare systems in Europe?

CRISPR-related gene therapy will reduce the burden on the healthcare system and provide a more effective allocation of healthcare resources. This therapeutic approach will improve access to healthcare. Extended life expectancy will lead to a decline in hospitalizations which will reduce the expenditure on public resources and provide significant socio-economic benefits. Improved quality of life and prevention of long-term complications will increase the financial contribution to society.

DISCLAIMER

The therapies described above are currently under development and are not available to patients neither in Europe, nor in Bulgaria.