Sickle cell disease is a group of inherited blood disorders that affect the shape and function of red blood cells. Red blood cells are normally round and flexible, but in people with sickle cell disease, they become sickle-shaped or C-shaped. These sickle-shaped cells can get stuck in blood vessels, blocking blood flow and causing pain, fatigue, and other serious health problems.

Symptoms of sickle cell disease can include:

• Painful episodes, called crises, that can last for days or even weeks
• Fatigue
• Shortness of breath
• Dizziness
• Jaundice (yellowing of the skin and eyes)
• Swelling of the hands and feet
• Anemia (a lack of red blood cells)
• Frequent infections

Types of Sickle Cell Disease

There are several different types of sickle cell disease, depending on the specific mutations in the haemoglobin gene. The most common type is sickle cell anaemia (HbSS), which occurs when a person inherits two copies of the gene mutation from each parent. Other types of sickle cell disease include sickle cell-beta thalassemia (HbSB), which occurs when a person inherits one copy of the sickle cell gene mutation and one copy of a beta-thalassemia gene mutation, and sickle cell-C disease (HbSC), which occurs when a person inherits one copy of the sickle cell gene mutation and one copy of a haemoglobin C gene mutation.

Causes of Sickle Cell Disease

Sickle cell disease is caused by a mutation in the haemoglobin gene. Hemoglobin is the protein in red blood cells that carries oxygen. The mutation causes the haemoglobin to be misshapen, which makes the red blood cells sickle-shaped.

2.1. Thalassaemia

Thalassaemia is a group of inherited blood disorders that affect the production of haemoglobin, a protein in red blood cells that carries oxygen. People with thalassaemia have less haemoglobin than normal, which can lead to anaemia and other health problems.

Types of Thalassaemia

There are two main types of thalassaemia:

• Alpha thalassaemia is caused by a mutation in the gene that produces the alpha globin chain of haemoglobin.
• Beta thalassaemia is caused by a mutation in the gene that produces the beta globin chain of haemoglobin.

Symptoms of Thalassaemia

The severity of thalassaemia symptoms depends on the type of thalassaemia and the severity of the mutation. Symptoms of thalassaemia can include:

• Fatigue
• Pale skin
• Shortness of breath
• Dizziness
• Slow growth
• Enlarged spleen

Causes of Thalassaemia

Thalassaemia is caused by a mutation in the gene that produces haemoglobin. Haemoglobin is made up of two globin chains, alpha and beta. Alpha thalassaemia is caused by a mutation in the gene that produces the alpha-globin chain, while beta thalassaemia is caused by a mutation in the gene that produces the beta-globin chain.

3. How Does the Therapy Work?

 3.1. Trial Results

• Sickle cell disease: 45 people received Casgevy. Only 29 of these patients had been in the trial long enough for the interim analysis on which the approval is based.
• All but one of these 29 trial participants had no severe pain crises for at least 12 months after treatment.
• Thalassaemia: The therapy has been administered to 54 persons with thalassaemia for the trial. Of them, 42 were in the trial long enough for the interim analysis. 3
• 9 of the 42 patients did not need a transfusion for at least 12 months after the treatment. The need for transfusion dropped by 70% in the other three.

4. Treatment Preparation and challenges

• Casgevy is a one-time treatment for which the doctor has to first collect blood stem cells from the bone marrow using a process called apheresis used to filter out the blood for different components.
• The cells are then sent to the manufacturing site where it takes about six months for them to be edited and tested.
• Before a transplant with the edited cells, the doctor gives a conditioning medicine for a few days to clear the bone marrow of other cells that will be replaced by the modified cells.
• The patient has to stay in the hospital for at least a month so that the edited cells take up residence in the bone marrow and start making red blood cells with normal haemoglobin.
• Side effects from the treatment are similar to those associated with autologous stem cell transplants, including nausea, fatigue, fever and increased risk of infection.
• While the therapy shows tremendous potential, the cost remains a significant challenge, with estimates suggesting it could be as high as $2 million per patient. 
• This poses accessibility issues, especially for individuals in poorer countries.
• However, experts believe that with more research and development, prices may decrease, and local manufacturing facilities can enhance affordability.

5. Conclusion

Casgevy's approval marks a significant milestone in Crispr-based therapy. While challenges exist, including pricing and accessibility, ongoing research and potential reductions in costs indicate a promising future for gene therapies. The working gene therapy for sickle cell disease with upcoming clinical trials in the pipeline.