On 31 January the NHS announced the approval CASGEVY, the first CRISPR gene therapy treatment for sickle cell disease. It will be offered at specialist NHS centres to treat patients who experience recurrent sickle cell crises but lack a suitable donor to undergo a stem cell transplant. The treatment, originally priced at £1.65 million per dose, will be made available to NHS patients thanks to an undisclosed discount from Vertex Pharmaceuticals and additional funding from the NHS Innovative Medicines Fund.
Sickle cell disease is a genetic condition that affects adult haemoglobin – the substance inside our red blood cells that gives blood its red pigment and transports oxygen throughout the body. The abnormal haemoglobin causes red blood cells to become rigid and crescent shaped, like a sickle. These misshapen red blood cells can clump together and block blood vessels, triggering episodes of severe pain that require morphine to manage. The disease can cause severe complications including strokes, blindness, organ failure, and death. Bone marrow transplants can cure sickle cell disease, but they are limited to patients with matching donors. Without proper medical care, this disease can significantly shorten both the duration and quality of a person’s life.
How does this gene therapy work?
When you are in the womb, your blood contains foetal haemoglobin which binds oxygen from your mother more effectively than adult haemoglobin. This is needed because the foetus competes with its mother’s cells for the oxygen stored in her blood. After birth, the BCL11A gene instructs the body to produce adult haemoglobin instead of foetal haemoglobin – that high affinity is no longer needed since the baby has direct access to oxygen through breathing. In sickle cell disease, this adult haemoglobin does not work properly, red blood cells are sickle shaped and can get stuck in blood vessels. Thus, the disease symptoms begin to emerge when children are around 6 months old.
CASGEVY is a gene therapy that works by editing the BCL11A gene. Your body’s own blood stem cells are collected and sent for editing. CRISPR/Cas9, a precise gene-editing technology that won the Nobel Prize in 2020, is used to find and edit parts of DNA in these cells to reduce the activity of the BCL11A gene. These edited cells are returned to your body, where they produce foetal haemoglobin instead of the defective sickle-prone adult haemoglobin.
The CASGEVY treatment begins with a week-long collection of stem cells from the patient’s blood. The collected cells then spend six months in the laboratory where they undergo genetic modification and extensive testing to ensure they function correctly. Before receiving these modified cells, the patient’s existing bone marrow must be cleared out. This happens during a hospital stay where patients are given medication to remove old bone marrow cells. Once cleared, the modified cells are infused back into the patient’s bloodstream in a single intravenous infusion. Finally, patients spend 4-6 weeks in the hospital as the new cells establish themselves in the bone marrow and begin producing healthy red blood cells.
Gene therapy targets genetic diseases at their source by modifying the genome of specific cells. The treatment delivers the functional gene to affected tissues, helping them produce proteins that were either previously missing or non-functional. Through a single dose, it has the potential to offer long-term to permanent results to previously incurable diseases. With the NHS approval of CASGEVY – the UK’s first CRISPR-based therapy for sickle cell disease – it is estimated that around 50 patients could receive this ground-breaking treatment annually. This represents a huge leap forward in the treatment of this life-threatening condition and represents the next generation of medicine.
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