Sickle Cell Disease (SCD)

The U.S. Food and Drug Administration recently approved two gene therapies, Casgevy and Lyfgenia, to treat SCD in people ages 12 and older. Casgevy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics and also approved in the U.K., is the first CRISPR-based therapy to have received regulatory approval in the U.S. Lyfgenia, manufactured by Bluebird Bio, doesn’t use CRISPR but depends on a viral vector to change blood stem-cells.

Background:

Genetic therapies have created a lot of hope for treating SCD, yet they require the same amenities still out of reach of those most affected by the disease.

About Sickle Cell Disease (SCD)

SCD is an inherited haemoglobin disorder in which red blood cells (RBCs) become crescent- or sickle-shaped due to a genetic mutation.
These RBCs are rigid and impair circulation, often leading to anaemia, organ damage, severe and episodic pain, and premature death.
India has the third highest number of SCD births, after Nigeria and the Democratic Republic of the Congo.

Access to treatment as a major issue

In 2023, the Government of India launched the National Sickle Cell Anaemia Elimination Mission, to eliminate SCD by 2047. At present, however, treatment and care for SCD remains grossly inadequate and inaccessible.
Example is the unavailability of the drug hydroxyurea. It lessens the severity of pain, reduces hospitalisations, and improves survival rates by increasing the size and flexibility of RBCs and lowering their likelihood of becoming sickle-shaped.
Blood transfusion is another important therapy for SCD, but its availability is limited to district-level facilities. Most block-level community health centres don’t offer them.
Bone marrow transplantation (BMT), is out of reach for most SCD patients due to the difficulty in finding matched donors, the high cost of the treatment at private facilities, and long waiting times in public hospitals.
In light of this, the application of the gene-editing technology called CRISPR (short for Clustered Regularly Interspaced Short Palindromic Repeats’) to treat SCD is important – for its novelty and promise but also for the health disparities it makes apparent.
India has approved a five-year project to develop CRISPR for sickle cell anaemia.
Under its Sickle Cell Anaemia Mission, the Council of Scientific and Industrial Research is developing gene-editing therapies for SCD.
Around Rs 34 crore has been allocated for this mission over 2020-2023.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)

It is originally a feature of the bacterial immune system. It forms the basis for this technology.
In a nutshell, the system in bacteria serves as a warehouse for past infections by storing a part of the viral genetic material and incorporating it into its own, so the next time it is attacked, the bacteria is capable of recognising the virus and destroying it. The bacteria, in short, is immunised when it employs the CRISPR system.
Researchers have adapted it as a tool to cut, delete, or add DNA sequences at precise locations, opening different windows to treat genetic disorders, develop drought resistant plants, modify food crops, or experiment with de-extinction projects involving the woolly mammoth and the dodo.