However, unlike ad, aav does not stimulate inflammation in the host. Gene therapy for thalassemia as a classic gene model for human genetics, aglobin gene has been extensively studied in the fields of gene structure, gene evolution, gene transcription and regulation. Gene therapy is showing promise for treating one of the most common genetic disorders. We believe these approaches will provide the potential to treat a broad range of serious conditions with the goal that. Beta thalassemia is one of the most common monogenic genetic diseases. Jan 01, 2005 making gene therapy a therapeutic option in. Of note, gene therapy in thalassemia mice 29, 31, 32 with. Mar 06, 2012 pretransplant clinical history of the first gene therapy patient with severe e 0thalassemia patient plb then 18 year old male with severe e 0 thalassemia and no hpfh or. K e y w o r d s allogeneic transplantation, anemia, bone marrow transplant, gene therapy. Gene therapy, by autologous transplantation of genetically modified hematopoietic stem cells, currently represents a novel therapeutic promise. Jan 01, 2015 the inheritance of alpha thalassemia is complicated by the fact that mutations in two different genes hba1 and hba2 are associated with the condition.
Bluebird bios gene therapy eliminates the need for blood transfusions in patients with. Gene therapy for betaglobinopathies, particularly betathalassemia and sickle cell anemia, hold much promise for the future, as a one time cure for these common and debilitating disorders. Dec 12, 2018 there are a handful of genetherapy drugs on the market, but sicklecell diseases role as an early genetherapy target, and the promise of that therapy, might attract interest in how best to. Overall, after decades of research, that included both successes and pitfalls, the path towards a permanent, donorirrespective cure for beta thalassemia patients is steadily becoming a realistic approach. Such mutationspecific repair by disruption of aberrant regulatory elements dare is highly efficient, but to date, no systematic analysis has been performed to evaluate diseasecausing mutations as. The us biotech company bluebird bio has obtained eu conditional market approval for a gene therapy that could remove the need for blood transfusions for people with the blood disorder beta thalassemia. Gene therapy for beta thalassemia could thereby represent the first largescale implementation of this intervention in developing countries. Gene therapy for a serious blood disorder called betathalassemia showed significantly improved outcomes among patients, without serious side effects, according to the results of two clinical trials published in the new england journal of medicine. Gene therapy for thalassemia shows promise northwestern. Pdf gene therapy in thalassemia and hemoglobinopathies. Kan cardiovascular research institute, institute of human genetics and department of medicine, university of california, san francisco, ca 94143. First gene therapy for beta thalassemia from bluebird bio. To secure the space in the bone marrow for the transduced. This gene therapy study is a singlearm, multisite, single dose, phase 3 study to evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation hsct using lentiglobin bb305 drug product in patients with transfusion dependent.
Persons with beta thalassemia major require chelation therapy for iron overload. Download this slideset for an expertcurated overview of gene therapy for. E 0thalassemia mutation transfusion dependent since age 3 225 ml rbcs kgyear for hb 10 gdl. Nov, 2009 gene therapy in thalassemia and hemoglobinopathies article pdf available in mediterranean journal of hematology and infectious diseases 11. Apr 19, 2018 after previously establishing that lentiviral transfer of a marked. Cells were collected from the bone marrow of a patient with. Pretransplant clinical history of the first gene therapy patient with severe e 0thalassemia patient plb then 18 year old male with severe e 0 thalassemia and no hpfh or. People have two copies of the hba1 gene and two copies of the hba2 gene in each cell. Thalassemia ucsf benioff childrens hospital oakland. As you prepare to use the tools in this kit, we want you to know that you are not alone. Called zynteglo, the gene therapy is aimed at treating people with betathalassemia who are over 12 years of age and have any but the most severe form of the condition. It is caused by more than 200 mutations of the betaglobin gene hbb and affects almost 288,000 people worldwide with 60,000 new cases per year. Gene therapy for betathalassemia major using autologous. Results of a study published wednesday show that 15 of 22 patients with beta thalassemia who got gene therapy.
Thalassemia treatment succeeds, with a caveat science. A guide to gene therapy because you or a loved one has a rare genetic disease. Recoding the stories of peoples lives requires a different way of treating disease. Molecular cloning the new edition buy now and save 30% paperback only limited time offer. Established in 1991, with more than 200 patients on active followup and over 800 patient visits every year, the center is one of the largest thalassemia programs in the country. Dec 11, 2009 gene therapy gene therapy researchers are approaching a key milestone. A young man who received new genes to repair blood cells no longer needs regular transfusions and, 2 years later, seems healthy. Despite the encouraging clinical results, current thalassemia gene therapy protocols are complex, involving the collection of hspcs from donorspatients by leukapheresis, in vitro culture, transduction with lentivirus vectors carrying a. It has been developed by bluebird bio and was given breakthrough therapy designation by the food and drug administration in february. Learn more about its symptoms and how its diagnosed. Dec 06, 2019 download this slideset for an expertcurated overview of gene therapy for. The goal of gene therapy for the treatment of betathalassemia is to. Apr 19, 2018 gene therapy scores success at treating thalassemia. Gene therapy in betathalassaemia and other hemoglobin.
The more severe the thalassemia, the less hemoglobin the body has, and the more severe the anemia may be. After purification, the hematopoietic stem cells hscs were maintained in culture for 34 h. At87q gene could substitute for longterm redcell transfusions in a patient with. Gene therapy for hemoglobin disorders journal of rare diseases.
It has been developed by bluebird bio and was given breakthrough therapy designation by the food and drug administration in february, 2015. Gene therapy scores success at treating thalassemia science. At87qglobin gene, formerly known as lentiglobin bb305 is a treatment for beta thalassemia, a rare and potentially debilitating blood disorder. There are a handful of genetherapy drugs on the market, but sicklecell diseases role as an early genetherapy target, and the promise of that therapy, might attract interest in. Passed on as an autosomal recessive trait, it disrupts the production of the hemoglobin beta chain, resulting in a more or less severe anemia. Aav mediated thalassemia gene therapy adenoassociated virus aav is often foun d in cells that are simultaneously infected with adenovirus ad. After destroying the affected persons bone marrow with a dose of chemotherapy a myeloablative conditioning. Gene therapy for a thalassemia was started in 1980.
The earliest assumption towards a molecular therapy for betathalassemia was the ex vivo gene addition strategy. Such mutationspecific repair by disruption of aberrant regulatory elements dare is highly efficient, but to date, no systematic analysis has been performed to evaluate diseasecausing mutations. Bringing hsc gene therapy to more patients will require not just the availability of autologous hscs, but of highquality vector and reliable, highvolume manufacturing of transduced cells. Advances in transplantation and gene therapy in transfusion. Fetal gene therapy of thalassemia in a mouse model xiaodong han, chin lin, judy chang, michel sadelain, and y. Thompson, md, mph, professor of pediatrics in the division of hematology. Thalassemia and sickle cell disease scd are the worlds two most widely disseminated hereditary hemoglobinopathies. 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. Thalassemia is due to a deficit or absent production of. The procedure involves collecting hematopoietic stem cells hscs from the affected persons blood.
Retroviral vectormediated gene transfer into hematopoietic stem cells provides a potentially curative therapy for severe. Congestive heart failure and abnormal heart rhythms can be associated with severe thalassemia. Current and future alternative therapies for betathalassemia. The international, multicenter trials were led by alexis a. Gene therapy gene therapy researchers are approaching a key milestone. Researchers have shown that gene therapy can help people with. The type of treatment a person receives depends on how severe the thalassemia is. One way to treat anemia is to provide the body with more red blood cells to carry oxygen. Betathalassemia treatment with gene therapy reduced. Thalassemia genetic and rare diseases information center. Gene therapy scores success at treating thalassemia. The inheritance of alpha thalassemia is complicated by the fact that mutations in two different genes hba1 and hba2 are associated with the condition. Apr 18, 2018 gene therapy is showing promise for treating one of the most common genetic disorders. After previously establishing that lentiviral transfer of a marked.
Gene therapy by either gene insertion or editing is an exciting curative. Gene therapy for betaglobinopathies, particularly beta thalassemia and sickle cell anemia, hold much promise for the future, as a one time cure for these common and debilitating disorders. Pdf gene transfer for betathalassemia requires gene transfer into hematopoietic stem cells using integrating vectors that direct regulated. The hscs then have a betaglobin gene added using a lentiviral vector.
Retroviral vector mediated gene transfer into hematopoietic stem cells provides a potential ly curative therapy for severe bthalassemia. Gene therapy for betathalassemia major using autologous hematopoietic stem cell genetically modified the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. More than 1,800 gene therapy trials have been conducted since then. This is because the mutant genes are wellknown and scientists have the ability to produce certain blood cells from stem cells in the lab. Northern californias comprehensive thalassemia center at childrens hospital oakland, delivers quality care to thalassemia patients. The us biotech company bluebird bio has obtained eu conditional market approval for a gene therapy that could remove the need for blood transfusions for people with the blood disorder betathalassemia.
The development of gene therapy for b hemoglobinopathies has been justi. Bluebird bio has been granted the goahead to market its gene therapy for the blood disorder. Clinical care options cco downloadable resource guide for the optimal management of patients with graftvshost disease gvhd. For some years now, gene therapy has been seen as a great promise for the cure of several serious diseases and in particular for genetic disorders. This study demonstrates that if gene therapy includes an adequate vector copy number in the drug product, the need for red cell transfusions can be reduced, and dyserythropoiesis characteristic of severe. Gene therapy for thalassemia normalizes hemoglobin. Bluebird bio wins european approval for beta thalassemia gene. Bluebird bio wins european approval for beta thalassemia. For each gene, one copy is inherited from the mother and one is inherited from the father. The retrovirus is the earliest and the most frequently used vector. Results of a study published wednesday show that 15 of 22 patients with betathalassemia who got gene therapy. Thalassemia is a blood disorder in which the body makes an abnormal form of hemoglobin. They appear to have controlled an inherited blood disorder called. The scope for thalassemia gene therapy by disruption of.
Bluebird bio wins european approval for beta thalassemia gene therapy. Aug 01, 2019 bluebird bio wins european approval for beta thalassemia gene therapy thursday, august 1, 2019 bluebird bios onetime gene therapy, zynteglo, has been cleared by e. Development of gene therapy for thalassemia ncbi nih. Beta thalassemia is usually inherited in an autosomal recessive manner, which means both copies of the hbb gene in each cell have mutations. Gene therapy in patients with transfusiondependent. Gene therapy in thalassemia and hemoglobinopathies article pdf available in mediterranean journal of hematology and infectious diseases 11. Overall, after decades of research, that included both successes and pitfalls, the path towards a permanent, donorirrespective cure for betathalassemia patients is steadily becoming a realistic approach. Alphathalassemia, a form of blood diseases caused by deletions in the. The earliest assumption towards a molecular therapy for beta thalassemia was the ex vivo gene addition strategy. It is an approach, as previously mentioned, that aims to cure genetic diseases. Successful gene therapy trials have generally utilized myeloablative doses of busulfan around 1216 mgkg. If you have thalassemia, or if you carry a thalassemia gene, consider talking with a genetic counselor for guidance if you want to have children.
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