World Sickle Cell Awareness Day: Can gene therapy be the silver bullet? An Indian start-up looks for a breakthrough

Sickle cell disease, caused by a mutation in the HBB gene, sees over 30,000 cases reported every year in India.

Sickle cell disease (SCD) and thalassemia major (TM) are two genetic disorders that affect a significant number of people in India every year.

Sickle cell disease is a chronic single-gene disorder that causes a debilitating systemic syndrome characterised by chronic anaemia, acute pain, organ infarction (tissue death), chronic organ damage (when an organ’s functioning is impaired), and a significant reduction in life expectancy.

Sickle cell disease, caused by a mutation in the HBB gene, sees over 30,000 cases reported every year in India.

This disease causes red blood cells to become sickle-shaped, which results in them becoming rigid and sticky, which often slows or blocks the blood flow, leading to a range of health problems.

During her budget speech earlier this year, Union Finance Minister Nirmala Sitharaman announced India's ambitious goal of eradicating sickle cell anaemia by 2047.

“Under a new scheme, the centre plans to screen 70 million Indians in affected tribal areas under the age of 40,” a health ministry official told Moneycontrol.

People with sickle cell disease often die young, particularly in regions with limited life-saving medical care.

Beta-thalassemia, also known as thalassemia major, is another inherited blood disorder that affects more than 10,000 people in India each year. This condition results in the body producing fewer healthy red blood cells, leading to anaemia, the need for regular transfusions every 2-4 weeks, and other disease and transfusion-related complications.

Both conditions result from mutations in genes that control the production of haemoglobin, a protein that carries oxygen throughout the body. These conditions can have a significant impact on a person’s quality of life and require ongoing medical care.

Currently, the only possible cure is bone marrow transplant, which is beset with challenges that make the treatment useful for less than 20 percent of patients suffering from either SCD or TM.

However, recent advances in gene therapy have provided hope for a potential cure for these disorders.

Gene therapy

Gene therapy is a type of treatment that involves modifying a person's genes to correct or treat a genetic disease.

It works by introducing healthy copies of a gene into a person's cells to replace or supplement the defective gene causing the disease, or by silencing the defective gene.

Gene therapy for sickle cell disease and thalassemia major involves introducing healthy copies of the affected gene into a person's cells to replace the faulty gene.

The therapy typically involves using a viral vector to deliver the transgene (healthy gene) to the patient's stem cells, and subsequently letting these cells grow back to produce healthy red blood cells, making the patient symptom free. A viral vector is a harmless virus used to deliver genetic material into cells.

The viral vector is modified to carry healthy genes, and once it enters the stem cells, it incorporates the new genes in the cell's DNA, allowing the cells to produce healthy haemoglobin. The vector’s self-replicating potential is deactivated.

Based on promising phase I and phase II data in US and Europe, Somerville-based Bluebird Bio, a biotechnology company, has got FDA’s approval to market its product, which goes by the brand name Zynteglo, to treat TM.

Genome engineering to treat SCD and TM

Alternatively, in recent years CRISPR Cas9-based genome editing to repair defective genes has gained a lot of attention due to its ease and precision. CRISPR is a gene-editing tool.

Based on promising phase I and II data, CRISPR Therapeutics and Vertex Therapeutics  shall soon be getting the licence to market their product using CRISPR Cas9-based genome editing to cure both SCD and TM.

Although both the above approaches are promising and give hope to millions of patients, they cost between Rs 18-25 crore, which puts them out of the reach of most of humanity.

To bring these treatments within the grasp of regular people, some companies have been trying to come up with state-of-the-art, affordable gene therapy solutions.

In India, Cellogen Therapeutics, a Delhi-based cell and gene therapy start-up, has made some progress in making gene editing affordable for SCD and TM patients.

According to the founders, the start-up has developed guide RNAs to target genomes and cause mutations in putative genes to treat sickle cell disease and thalassemia. A guide RNA is a piece of RNA that functions as a guide for DNA-targeting enzymes. A putative gene is a segment of DNA that is like a gene.

“Cellogen Therapeutics is dedicated to developing the necessary infrastructure and expertise to deliver this cost-effective therapy to patients in need, especially in India, where the burden of these diseases is significant and existing treatments are limited,” said Gaurav Kharya, Founder and Director, Cellogen Therapeutics.

The Cellogen founders say they have filed a patent for their technology that treats both sickle cell disease and beta-thalassemia.

The product is expected to cost around Rs 35-40 lakh. The company is yet to conduct field trials and apply to the DCGI (Drugs Controller General of India) for approval.