Context:

• Recently, The UK drug regulator approved a gene therapy (Casgevy therapy) to cure sickle cell disease and thalassemia, a landmark breakthrough.

What is Casgevy Therapy?

• This is the first licensed therapy in the world based on gene editing technology CRISPR-Cas9.
• It  is a one-time therapy that edits the faulty gene that leads to these blood disorders, potentially curing the person for life.

How does the therapy work?

• Errors in the hemoglobin gene cause both sickle cell disease and thalassemia.
• The therapy uses the patient’s own blood stem cells, which are precisely edited using Crispr-Cas9. 
• The therapy targets a gene called BCL11A, which is crucial for switching from fetal to adult hemoglobin.
• The therapy uses the body’s mechanisms to produce more foetal hemoglobin, alleviating the symptoms of the two conditions.

How is the therapy prepared and given?

• Apheresis:  The first step is extracting blood stem cells from the bone marrow and filtering the blood for different components. 
• Harvesting and Editing: The cells are then sent to the manufacturing site, which takes about six months to be edited and tested.
• Conditioning: 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.
• Transplantation: The patient has to stay in the hospital for at least a month so that the edited cells reside in the bone marrow and start making red blood cells with normal haemoglobin.
• Side effects: similar to those associated with autologous stem cell transplants, including nausea, fatigue, fever, and increased risk of infection.

What are the challenges of this treatment?

• High Cost of Treatment:  a high proportion of people with these conditions live in poorer countries and are unlikely to be able to afford the therapy 
  • Estimates suggest it could be as much as $2 million per patient, which aligns with other gene therapies. 
• Absence of Local Manufacturing Facilities: The harvested blood stem cells must be sent across countries.
• Earlier Treatment: Permanent treatment has been a bone marrow transplant.
  • Donor rejection is the major challenge.

About sickle cell disease:

• Genetic Disorder: The genetic error in sickle cell disease leads to red blood cells assuming a crescent shape. (See image) 
• Unlike the disc-shaped normal cells, the sickle-like cells cannot move around easily in the vessels, resulting in blocked blood flow. 
• Effects: severe pain, life-threatening infections, anemia, or a stroke.
• Prelevance in India: An estimated 30,000-40,000 children in India are born with the disorder every year.
• Symptoms: The symptoms manifest in people who inherit a pair of damaged genes from both parents. Those who carry only one copy of the gene from one parent can lead a normal life.

About Thalassaemia: 

• Thalassemia is an inherited (i.e., passed from parents to children through genes) blood disorder caused when the body doesn’t make enough of a protein called haemoglobin.
• Thalassaemia leads to low levels of haemoglobin and shows symptoms like fatigue, nausea, shortness of breath, and irregular heartbeats. 
• People with the condition need blood transfusions throughout their life. The transfusions also lead to excess iron accumulation in the body, which needs chelation.
• India also has the largest number of children with thalassaemia major in the world about 1-1.5 lakh.

Source: Indian Express