Sickle cell anemia (SCA), a hereditary blood disorder, has long been a challenge for both doctors and patients. This condition affects millions globally, especially in places where malaria is prevalent. In India, about 30,000 children are born every year.
Sickle cell anemia is caused by a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. Hemoglobin is the protein in red blood cells responsible for carrying oxygen to different parts of the body. The mutation leads to the production of abnormal hemoglobin, known as hemoglobin S (HbS). Under low oxygen conditions, HbS molecules tend to polymerise, forming rigid structures that distort red blood cells into a sickle shape. These sickle-shaped cells are less flexible and can block small blood vessels, causing painful vaso-occlusive crises and can lead to other severe complications.
Traditional treatments have primarily focused on managing symptoms and preventing complications, but recent advancements in our understanding of sickle cell anemia and innovations in medical technology have led to the development of several promising new therapies. These therapies aim not only to manage symptoms but also to address the underlying genetic cause of the disease.
1. Gene Therapy
Gene therapy represents one of the most promising advancements in the treatment of sickle cell anemia. This approach involves modifying the patient’s own hematopoietic stem cells to correct the genetic defect responsible for the disease. Two main strategies are being explored:
Gene addition: This method involves adding a normal copy of the HBB gene to the patient’s stem cells using a viral vector. The modified stem cells are then reintroduced into the patient’s body, where they produce normal hemoglobin. Early clinical trials have shown promising results, with some patients achieving significant improvements in symptoms and quality of life.
Gene editing: CRISPR-Cas9 technology allows for precise editing of the genome to correct the sickle cell mutation or reactivate the production of fetal haemoglobin. By targeting genes like BCL11A, which suppress fetal haemoglobin production, researchers can increase HbF levels and reduce the severity of the disease. Initial trials using CRISPR for sickle cell anemia have yielded encouraging outcomes.
2. Voxelotor
Voxelotor is a novel oral medication that directly targets the sickling process of red blood cells. It works by increasing the affinity of hemoglobin for oxygen, which stabilizes the red blood cells and prevents them from adopting the sickle shape. Approved by the FDA in 2019, Voxelotor is also available in India and is approved for children aged 4 or older. This medication provides a new option for patients who may not respond adequately to traditional therapies like hydroxyurea.
3. L-GlutamineL
Glutamine is an amino acid that has been repurposed as a treatment for sickle cell anemia. It helps reduce oxidative stress in red blood cells, which can contribute to sickling and cell damage. Clinical trials have demonstrated that L-glutamine can reduce the frequency of pain crises and hospitalizations in patients with sickle cell anemia.
4. Anti-Sickling Agents
Several new drugs that directly target the sickling process of red blood cells are currently in development. These anti-sickling agents aim to prevent the polymerisation of HbS and maintain the flexibility of red blood cells. Some of the promising drugs include inclacumab and crizanlizumab.
Research is ongoing to optimise the existing treatments and to develop new treatment approaches. Some doctors are using combination therapies that integrate multiple treatment modalities to better manage the disease.
Though the advancements in sickle cell anemia therapies are promising, it is important to ensure the accessibility and affordability of these treatments, particularly in low-to-middle-income countries, where the disease is most prevalent.
(The author, Dr. Gaurav Kharya is director, Center for Bone Marrow Transplant and Cellular Therapy, Indraprastha Apollo Hospital.)
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