- Thalassemia is a genetically transmitted (i.e., handed from parents to children) blood illness that develops when the body doesn’t produce enough hemoglobin, a crucial component of red blood cells. With blood transfusions and chelation treatment, thalassemia can be successfully treated and controlled.
- There are two main types of thalassemia:
- α-thalassemia (or alpha thalassemia) occurs when a gene or genes related to the α-globin protein are missing or changed (mutated), and
- β-thalassemia (or beta thalassemia) occurs when similar gene defects affect production of the β-globin protein.
- Thalassemia’s are clinically divided into Thalassemia Major (TM), Thalassemia Intermedia (TI) and Thalassemia Minor or Trait according to severity. Thalassemia Major (TM) and the severe form of Thalassemia Intermedia (TI) constitute the major burden of disease as management of both requires lifelong blood transfusions and iron chelation.
- There are around 1 to 1.5 lakh children in India who have ß (beta) thalassemia major, making it the country with the highest number of carriers worldwide. Thalassemia major affects around 10,000–15,000 newborns annually.
Prenatal testing is one of the screening processes, which is done before the baby is born. To determine whether thalassemia is present, the following tests are used:
- Chorionic villus sampling: Usually carried out between weeks 11 and 14 of pregnancy. Often via the mother’s belly, a little sample of placental tissue is removed for further analysis using a thin needle.
- Amniocentesis: This procedure involves putting a little sample of the fluid around the developing fetus into the mother’s uterus via her stomach, usually during the 16th week of pregnancy. The fluid contains some of the baby’s cells, allowing for thalassemia screening.
Even if thalassemia is not preventable, Prenatal testing, preimplantation genetic diagnosis, parental genetic testing for the existence of the thalassemia gene, and public education and awareness campaigns regarding thalassemia can reduce the risk.
MANAGEMENT FOR THALASSEMIA MAJOR ARE:
- Blood transfusion therapy with packed red blood cells (pRBCs)
- Iron chelation for iron overload
- Monitoring of complications due to the disease and their treatment
- Management of complications (endocrine, cardiac, skeletal etc.),
- Bone marrow transplantation (BMT)/ Hematopoietic stem cell transplant (HSCT)
- Psychological support.
LATEST CLINICAL UPDATE IN THALASSEMIA
- IN UTERO HEMATOPOIETIC STEM CELL TRANSPLANTATION : Participants would undergo bone marrow harvest and an in-utero transfusion combined with maternal stem cells.
- Two patients had been transplanted in this clinical trial, and both are thriving toddlers.
- GENE EDITING THERAPY: Exa-cel, formerly known as CTX001™, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with transfusion dependent thalassemia (TDT) or Sickle Cell Disease (SCD, in which a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. The US FDA granted exagamglogene autotemcel (exa-cel) a rolling review for the potential treatment of TDT and SCD.
- PYRUVATE KINASE ACTIVATOR: Betibeglogene autotemcel (beti-cel) is a one-time gene therapy by Bluebirdbio, that adds functional copies of a modified form of the β-globin gene (β A-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once a patient has the β A-T87Q-globin gene, they have the potential to produce HbA T87Q, which is gene therapy-derived adult hemoglobin (Hb), at levels that may eliminate or significantly reduce the need for transfusions.
- The U.S. Food and Drug Administration (FDA) has approved ZYNTEGLO® (betibeglogene autotemcel), a one-time gene therapy to treat patients with beta-thalassemia who require regular red blood cell (RBC) transfusions on 17 August 2022.
- It was earlier given conditional approval by EMA, However due to commercial reasons it was withdrawn.
- ERYTHROID MATURATION AGENTS: Luspatercept is a fusion protein consisting of the extracellular domain of activin receptor type IIB fusion protein and the Fc-part of human immunoglobulin G1 (IgG1) by BMS. US FDA Approved the drug for the treatment of Anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions on November 8, 2019
- GENE SILENCING THERAPY: SLN124 is a gene ‘silencing’ therapy by Silence Therapeutics – one that is designed to temporarily block a specific gene’s message that would otherwise trigger an unwanted effect. In this case, SLN124 aims to temporarily ‘silence’ TMPRSS6, a gene that prevents the liver from producing a particular hormone that controls iron levels in the body – hepcidin. As hepcidin increases, iron levels in the blood are expected to decrease, which could in turn allow more healthy red blood cells to be produced, thereby improving anemia.
- SLN124 has demonstrated proof of concept in healthy volunteers and is being evaluated in a phase 1 study in patients with non-transfusion dependent thalassemia.
- SLN124 has rare pediatric disease and orphan drug designations for beta-thalassemia.