Gene therapy for transfusion dependent beta-thalassemia is based on the autologous transplantation of hematopoietic stem cells (HSCs) engineered by lentiviral vectors expressing a transcriptionally regulated human beta-globin gene.Gene therapy (GT) could represent an alternative to HSCT with the following potential advantages: use of autologous stem cells, tailored conditioning with no need for immune suppression post GT, no risk of GVHD or rejection.Our contribution to this field was devoted to the clinical development of a gene therapy protocol based on the high-titer vector GLOBE, a 3 rd generation self-inactivating lentiviral vector encoding for the human beta globin gene.
What is the genetic cause of beta thalassemia?
Sep 23, 2019 · Indeed, genetic treatment of beta-thalassemia has been very early singled out as one of the most promising areas for future gene therapies by the American Society of Gene and Cell Therapy. 13. Open in a separate window. Figure 1. Schematic representation of the classic gene addition protocol for the gene therapy of beta-thalassemia.
How do you treat beta thalassemia?
Apr 01, 2016 · Two main research directions based on gene editing have emerged in the globin field, one aiming to repair the β-globin gene ( HBB) and the other to reactivate the γ-globin gene ( HBG ), which is silenced after birth but is sometimes capable of compensating for a β-gene defect if it remains expressed at a sufficient level. HBB gene repair
What is the treatment for heterozygous beta thalassaemia?
Genetic therapy for beta-thalassemia: from the bench to the bedside. Beta-thalassemia is a genetic disorder with mutations in the β-globin gene that reduce or abolish β-globin protein production. Patients with β-thalassemia major (Cooley's anemia) become severely anemic by 6 to 18 months of age, and are transfusion dependent for life, while those with thalassemia int ….
Is there any treatment for beta thalassemia major?
Beta-thalassemia is caused by one or more mutations in the beta-globin gene. The absence or reduced amount of beta-globin chains causes ineffective erythropoiesis which leads to anemia. Methods: Beta-thalassemia has been further divided into three main forms: thalassemia major, intermedia, and minor/silent carrier.
How is gene therapy used to treat beta thalassemia?
β-thalassemia gene therapy is based on the transfer of a human β-globin gene into autologous HSCs, which resolves the absence of compatible donors and eliminates the risk of GVHD and graft failure associated with allogeneic BMT.Oct 1, 2021
What type of gene therapy is used for thalassemia?
Called Zynteglo, the gene therapy is aimed at treating people with beta-thalassemia who are over 12 years of age and have any but the most severe form of the condition. Patients with beta-thalassemia often depend on receiving blood transfusions for their whole lives.Apr 6, 2019
What current research is being done to develop a cure for thalassemia?
Scientists are working to develop a gene therapy that may offer a cure for thalassemia. Such a treatment might involve inserting a normal beta globin gene (the gene that is abnormal in this disease) into the patient's stem cells, the immature bone marrow cells that are the precursors of all other cells in the blood.Dec 27, 2013
Which technology is applied in treating beta thalassemia?
In the past few years, CRISPR technology has been tested for treating several diseases. For instance, CRISPR gene therapy has made huge strides for treating beta thalassemia and sickle cell anemia—inherited blood disorders caused by mutations in the gene encoding hemoglobin.
Does gene therapy work for thalassemia?
Adding a functional gene to defective blood stem cells is a successful therapy for patients with severe beta thalassemia, according to an international phase-3 clinical trial led by Ospedale Pediatrico Bambino Gesù in Rome, whose results have been published in the New England Journal of Medicine.Jan 26, 2022
Can thalassemia be cured by gene therapy?
Depending upon whether the genetic defects or deletion lies in transmission of α or β globin chain gene, thalassemias are classified into α and β-thalassemias. Thus, thalassemias could be cured by introducing or correcting a gene into the hematopoietic compartment or a single stem cell.
What is gene therapy simple definition?
Overview. Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your DNA — the code that controls much of your body's form and function, from making you grow taller to regulating your body systems. Genes that don't work properly can cause disease.
What do you know about gene therapy?
Gene therapy is a technique that modifies a person's genes to treat or cure disease. Gene therapies can work by several mechanisms: Replacing a disease-causing gene with a healthy copy of the gene. Inactivating a disease-causing gene that is not functioning properly.Jul 25, 2018
What does the HBB gene do?
The HBB gene provides instructions for making a protein called beta-globin. Beta-globin is a component (subunit) of a larger protein called hemoglobin, which is located inside red blood cells.
How is CRISPR used in gene therapy?
With other versions of CRISPR, scientists can manipulate genes in more precise ways such as adding a new segment of DNA or editing single DNA letters. Scientists have also used CRISPR to detect specific targets, such as DNA from cancer-causing viruses and RNA from cancer cells.Jul 27, 2020
How does gene therapy treat sickle cell anemia?
Gene therapy in sickle cell works by knocking down the expression of the BCL11A gene to flip the switch back to fetal hemoglobin, simultaneously increasing fetal hemoglobin, which does not sickle, and directly reducing sickling hemoglobin.
How does gene therapy treat cystic fibrosis?
The treatment uses a type of virus called a lentivirus to deliver a healthy copy of a gene called CFTR, which causes cystic fibrosis when it carries a mutation. The gene therapy will be given by inhalation to better target the right cells.Aug 6, 2018
What is the genetic therapy for beta thalassemia?
Genetic therapy for beta-thalassemia: from the bench to the bedside. Beta-thalassemia is a genetic disorder with mutations in the β-globin gene that reduce or abolish β-globin protein production. Patients with β-thalassemia major (Cooley's anemia) become severely anemic by 6 to 18 months of age, and are transfusion dependent for life, ...
What is beta thalassemia?
Beta-thalassemia is a genetic disorder with mutations in the β-globin gene that reduce or abolish β-globin protein production. Patients with β-thalassemia major (Cooley's anemia) become severely anemic by 6 to 18 months of age, and are transfusion dependent for life, while those with thalassemia int ….
What is the purpose of gene therapy?
Gene therapy holds the promise of "fixing" one's own bone marrow cells by transferring the normal β-globin or γ-globin gene into hematopoietic stem cells (HSCs) to permanently produce normal red blood cells.
How long does it take for a patient to become anemic?
Patients with β-thalassemia major (Cooley's anemia) become severely anemic by 6 to 18 months of age, and are transfusion dependent for life, while those with thalassemia intermedia, a less-severe form of thalassemia, are intermittently or rarely transfused.
BETA-THALASSEMIA TREATMENTS
As research continues to evolve, so does our understanding of beta (β)-thalassemia, and new treatment options are being developed.
Prenatal Screening and Genetic Counseling
Because beta-thalassemia is a genetic disease × Genetic disease a disease that is caused by a genetic change , it can be identified and diagnosed through prenatal screening. This can provide early diagnosis and allow people to better understand how beta-thalassemia can be managed.
Medical Evolutions
Currently, there are medications adults can pair with red blood cell transfusions to help address some of the symptoms associated with beta-thalassemia.
Gene Therapy
Similar to a donor stem cell (or allogeneic) transplant, gene therapy is another treatment option that has the potential to treat beta-thalassemia in some patients. Unlike a stem cell transplant, however, gene therapy uses a patient's own cells.
What is thalassaemia major?
Homozygous β-thalassaemia or thalassaemia major is a genetic disorder of the blood caused by the inheritance1 of two mutated (defective, non-functional) β-globin genes3 (one from each parent). As a result of this genetic defect, the body can only produce little or no normal adult haemoglobin (HbA), the vital oxygen carrying protein of the body.
When was Thalassaemia International Federation founded?
Thalassaemia International Federation is an NGO founded in 1986 by a small number of patients and families representing National Thalassaemia Associations in Cyprus, Greece, UK, USA and Italy, countries in which these diseases have been recognised as an important matter for public health and where the first programmes for prevention and management were implemented.
How does genome editing help with genetic diseases?
It allows scientists in the lab to address the cause and not just the symptoms of genetic diseases by performing a sort of genetic surgery for correcting DNA defects. Technically, genome editing tools are able to change genes by adding, replacing and/or removing sections of DNA, thus correcting the mutation responsible for causing the disease. The latest genome editing system is called CRISPR/Cas9. Published information relates this to faster, cheaper, and more accurate technology than any other system. It is also technically easy to use, which means that may be accessible to a large number of scientists and laboratories. Importantly, this technology is still being developed and it may be some years before genome editing could directly benefit rare disease patients including thalassaemia patients.
What is zyntegalotm?
ZYNTEGLOTM is the new product of the work of Bluebird Bio Inc and is the new therapeutic option for patients with β-thalassaemia major based on the transfer of a functional β-globin gene into the patients’ cells. Using a lentiviral vector, functional copies of a modified β-globin gene are added into a patient’s own stem cells, thereby addressing the underlying genetic cause of the disease.
What is the cause of beta thalassemia?
Beta-thalassemia is an inherited disease caused by defects in the beta-globin gene. This gene produces an essential part of the hemoglobin protein, which, in the form of red blood cells, carries life-sustaining oxygen throughout the body.
Can gene therapy be used for sickle cell anemia?
Scientists have designed what appears to be a powerful gene therapy strategy that can treat both beta-thalassemia disease and sickle cell anemia. They have also developed a test to predict patient response before treatment.
What companies are involved in gene therapy?
Companies like Novartis AG, UniQure N.V. Spark Therapeutics LLC; Bluebird Bio; Kite Pharmaceuticals, Acceleron Pharma Gilead Sciences, Inc. and many others are successfully involved in advancing the Beta- thalassemia market with vast pipeline products.
Is Bluebird Bio a gene therapy?
Recently BlueBird Bio has received the approval from the US FDA for its lentiviral vector, LentiGlobin BB305 (zynteglo) is one-time gene therapy . It was granted Breakthrough Therapy designation by the US FDA in 2015. Recently, it has received conditional marketing authorization valid pan-Europe. The company started Phase III trials in 2017 to evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 drug products. The trials are expected to end by 2021.
