Sickle cell breakthrough

Subject : Science and Tech

Section: Health

Context: The UK drug regulator last week approved a gene therapy for the cure of sickle cell disease and thalassaemia

More about the news:

The UK drug regulator recently granted approval for a groundbreaking gene therapy named Casgevy, designed to cure sickle cell disease and thalassaemia.
This marks a historic breakthrough, as Casgevy is the world’s first licensed therapy based on the Crispr-Cas9 gene editing technology, which was honoured with a Nobel Prize in 2020.
The innovative “genetic scissors” of Crispr-Cas9, introduced in 2012, have revolutionized biotechnology.
Casgevy operates by editing the faulty gene responsible for these blood disorders, offering the potential for a lifelong cure.
This approval signifies a significant departure from the previous reliance on bone marrow transplants, which necessitated a closely matched donor for a permanent treatment.
The advent of Casgevy represents a transformative step in the field of medical science, showcasing the power and potential of gene editing technology in addressing genetic diseases.

How does the therapy work:

The gene therapy, Casgevy, addresses both sickle cell disease and thalassaemia by targeting errors in the gene for hemoglobin, a crucial protein in red blood cells responsible for oxygen transport.
Utilizing the Crispr-Cas9 technology, the therapy edits the patient’s own blood stem cells, specifically focusing on the BCL11A gene.
This gene is vital for the transition from fetal to adult hemoglobin.
By leveraging the body’s natural mechanisms, the therapy prompts increased production of fetal hemoglobin, which lacks the abnormalities associated with adult hemoglobin.
This innovative approach aims to alleviate the symptoms of both conditions by promoting the production of healthier hemoglobin variants.

What are sickle cell disease and thalassaemia:

The genetic anomaly in sickle cell disease causes red blood cells to adopt a crescent shape, hindering their movement in vessels and resulting in blocked blood flow.
This can lead to severe pain, life-threatening infections, anemia, or stroke.
In India, an estimated 30,000-40,000 children are born with this disorder annually.
Symptoms appear in individuals inheriting damaged genes from both parents, whereas those with only one affected gene can lead a normal life.
Thalassemia, similarly, manifests when both parents pass on affected genes, causing severe anemia.
India also holds the world’s largest number of children with thalassemia major, approximately 1-1.5 lakh, who require lifelong blood transfusions leading to iron accumulation and necessitating chelation therapy.

What have the trials shown so far

In the clinical trial for Casgevy, a gene therapy for sickle cell disease, 45 participants were treated, with 29 individuals available for the interim analysis that led to approval.
Almost all of these 29 patients experienced no severe pain crises for a minimum of 12 months post-treatment.
For thalassemia, 54 individuals received the therapy, and 42 were part of the trial’s interim analysis.
Of these, 39 did not require a transfusion for at least 12 months after treatment, and the need for transfusion decreased by 70% in the remaining three participants.
These promising results highlight the potential efficacy of Casgevy in addressing both sickle cell disease and thalassemia.

How is the therapy prepared and given:

Casgevy, a one-time gene therapy, involves a multi-step process.
Initially, the doctor collects blood stem cells from the bone marrow through apheresis, a method used to filter out blood components.
The harvested cells are then sent to a manufacturing site where editing and testing take approximately six months.
Prior to the transplant with edited cells, the patient receives a conditioning medicine for a few days to clear the bone marrow of other cells, which will be replaced by the modified cells.
For about a month, the patient stays in the hospital to facilitate the integration of edited cells into the bone marrow, enabling the production of red blood cells with normal hemoglobin.
The side effects of this treatment resemble those associated with autologous stem cell transplants and may include nausea, fatigue, fever, and an increased risk of infection.
Despite potential side effects, Casgevy offers a promising one-time solution for addressing genetic blood disorders.

What are the challenges of this treatment

The newly approved gene therapy, Casgevy, faces potential challenges due to its anticipated high cost, which could reach up to $2 million per patient, consistent with the pricing of other gene therapies.
The absence of local manufacturing facilities poses an additional hurdle, necessitating the shipment of blood stem cells across countries.
While the approval of this Crispr-based therapy is seen as a significant advancement, the high pricing poses a major obstacle, particularly for individuals in poorer countries where a significant portion of those affected reside.