Cystic fibrosis is a severe autosomal recessive disease affecting one in. Cystic fibrosis cf is a common, lethal, genetic disease and is caused by mutations in the cystic fibrosis transmembrane conductance regulator cftr. Cystic fibrosis transmembrane regulator replacement therapy cystic fibrosis transmembrane regulator pharmacotherapy stimulation of alternative chloride channels inhibition of sodium absorption airway rehydration summary since the detection of the underlying gene defect, our knowledge of how the genetic mutations in. Clinically this leads to difficulties breathing and frequent lung infections. Delivery and expression of a single copy of a normal cftr gene leads to stable correction of the cl channel regulation defect present in cf epithelial cells. Prospects for gene therapy in cystic fibrosis archives of. Feb 26, 2019 please use one of the following formats to cite this article in your essay, paper or report. Cystic fibrosis cf is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Cystic fibrosis cf is a recessive disease associated with loss of function mutations in the cf. Cystic fibrosis is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator cftr channel, causing viscous secretions. Gene therapy trials for cystic fibrosis sciencedirect. These have largely been single dose to either nose or lower airway and have. A randomised, doubleblind, placebocontrolled trial of repeated nebulisation of nonviral cystic fibrosis transmembrane conductance regulator cftr gene therapy in patients with cystic fibrosis. The field of gene therapy has progressed rapidly since the cystic fibrosis transmembrane conductance regulator cftr gene was cloned.
Gene delivery systems gds play a central role in the development of gene therapy strategies for cystic fibrosis cf. Since cloning of the cftr gene more than 20 years ago a large number of preclinical and clinical cf gene therapy studies have been performed and a vast amount of. Cystic fibrosis is a genetic disease that causes mucus to build up in a patients lungs. If this observation is reproducible, it could herald a new and effective treatment for the gastrointestinal pathology associated with cystic fibrosis, although any. A randomised, doubleblind, placebocontrolled trial of repeated nebulisation of. Gene therapy may be a viable approach for treating or preventing lung disease caused by cystic fibrosis cf, suggests new research. Making progress toward gene therapy for cystic fibrosis. Cystic fibrosis patients are, in many cases, unrealistically pinning their hopes upon gene therapy which, as was pointed out in an editorial in thelancet, may have been oversold to research funding bodies and to the general public. Viral vectors, animal models, and cellular targets for. Cystic fibrosis what is cystic fibrosis cystic fibrosis cf is a chronic, progressive.
Since the discovery of the gene encoding cystic fibrosis cf, there has been much excitement about the possibility of gene therapy, which has now reached the stage of phase i clinical trials in adults. When there is a mutation or alteration in the genetic instructions, the production of the cftr protein may be affected. Sep 20, 2016 gene therapy may be a viable approach for treating or preventing lung disease caused by cystic fibrosis cf, suggests new research. Muellers gene therapy strategies on cystic fibrosis.
Yet, physical and host immune barriers in the lung present. Cystic fibrosis is the lethal inherited disease that effects lungs pancreas sweat glands characterized by the production of abnormally viscous mucus by the affected glands fibrous scar tissue develops in the pancreas. The sweat glands and the reproductive system are also usually involved. Cystic fibrosis what is cystic fibrosis cystic fibrosis cf is a chronic, progressive, and frequently fatal genetic inherited dis ease of the bodys mucus glands. The present invention comprises gene therapy for treating cystic fibrosis cf. It is the most common type of chronic lung disease in children. Although unknown questions still remain regarding the cellular targets in the lung that are required or sufficient to complement cf lung disease, the field is now well positioned to tackle these. The gtc announced results from the phase 2b clinical trials of its wave 1 gene therapy product in 2015. Cystic fibrosis gene therapy in the uk and elsewhere ncbi. In people with cystic fibrosis, mutations in the cftr gene can result in no protein, not enough protein, or a protein being made incorrectly. Advances in gene therapy for cystic fibrosis lung disease. J m wilson institute for human gene therapy, wistar institute, philadelphia, pennsylvania, 19104, usa. The first gene therapybased drug gendicine, an adenovirus ad carrying the p53 tumor suppressor gene for the treatment of head and neck cancer, was only approved in china.
The report of the first patients with cystic fibrosis cf to receive cystic fibrosis transmembrane conductance regulator gene cftr therapy appeared in 1993, and since then there have been. The principal cause of morbidity and mortality in cystic fibrosis cf is pulmonary disease, so the focus of new treatments in this condition is primarily targeted at the lungs. Gene therapy for cystic fibrosis proceedings of the. Cystic fibrosis cf is the most common, lifeshortening genetic disease in. Today, researchers struggle to develop a safe, effective gene therapy, as well as other, more traditional therapies. Please use one of the following formats to cite this article in your essay, paper or report. Basic research suggests that cf gene therapy is feasible, but major technological challenges must be addressed before clinical applications are likely to succeed. A demonstration using mouse models that successful gene therapy for cystic fibrosis requires only partial gene correction. To date, more than 20 clinical trials have been conducted with a variety of. Direct delivery of the cystic fibrosis transmembrane conductance regulator cftr gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Pdf gene therapy for the treatment of cystic fibrosis researchgate. A new method of gene delivery has been developed that uses compacted dna nanoparticles to penetrate the nuclear membrane. Gene therapy has been defined as the introduction or alteration of genetic material within a cell or organism with the intention of curing or treating a disease.
Cystic fibrosis cf is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator cftr, a cyclic ampactivated chloride channel. Gene therapy for the treatment of cystic fibrosis this article provides an in depth look into the novel treatment available for cystic fibrosis. Prospects for gene therapy in cystic fibrosis archives. The cystic fibrosis transmembrane conductance regulator cftr gene contains the instructions for making the cftr protein. Reduced or absent campmediated chloride transport in epitheliallined organs.
In july 2015, the results of an eagerly anticipated. It is the most common type of chronic lung disease in children and young adults, and may result in early death. Further, these systems are important tools in studies with cultured cells and in animal models. Lessons learned from early gene therapy attempts with raav in the cf lung have guided thinking for the testing of next generation vector systems. Gene therapy is currently being evaluated for a wide range of acute and chronic lung diseases including acute respiratory distress syndrome ards, cancer, asthma. Gene therapy treatment for cystic fibrosis may be possible by 2020, scientists say. Gene therapy for cf the cftr gene, mutations of which result in cf, was discovered in 1989. Today, researchers struggle to develop a safe, effective gene. Since 1989 when the gene responsible for cystic fibrosis was cloned and designated the cystic fibrosis transmembrane conductance regulator cftr gene.
As with any new development of clinical medicine, the development of somatic gene therapy protocols for cystic fibrosis is likely to be incremental. We use gene therapy to express cftr in the lung or correct the tcell phenotype by gene therapy or calcium channel modulators. Cftr normally acts as a cyclic adenosine monophosphate. Lessons learned from early gene therapy attempts with raav in the cf lung have guided thinking for the testing of nextgeneration vector systems. The gtc are currently seeking a pharmaceutical partner to fund phase 3 trials of. With improvements in nutritional therapy, antibiotics, and chest phys. This gene encodes a protein called the cf transmembrane conductance regulator cftr, which is situated in the apical membrane of epithelial cells and.
Viral vectors, animal models, and cellular targets for gene. While treatment advances have increased the life expectancy of patients, most of them only live to the. By 1993, gene therapy trials to treat people with cf began. If this observation is reproducible, it could herald a new and effective treatment for the gastrointestinal pathology associated with cystic fibrosis. Repeated nebulisation of nonviral cftr gene therapy in patients with cystic fibrosis. Delivery and expression of a single copy of a normal cftr gene leads to stable correction of the cl channel. Cystic fibrosis cf is an autosomal recessive disease caused by mutations in the cystic fibrosis. Gene therapy for cystic fibrosis what is cystic fibrosis. I was intrigued by larson and colleagues claim march 1, p 6191 that they have reversed the cystic fibrosis phenotype in mice by transient infection with a cystic fibrosis transmembrane. Gene therapy for cystic fibrosis article pdf available in the lancet 3499060. Pdf gene therapy for cystic fibrosis lung disease researchgate. Ideally, gene therapy could repair or replace the defective gene. New approaches to genetic therapies for cystic fibrosis. Further, these systems are important tools in studies with cultured cells.
Gene therapy as a potential cure for cystic fibrosis. Challenges and strategies for cystic fibrosis lung gene. Working with cf pigs, the researchers have shown that two. It is the most common fatal genetic disease in the developed world. Cystic fibrosis questionnaire revised qualityoflife. Basic research suggests that cf gene therapy is feasible, but major. Since the cloning of the cystic fibrosis transmembrane conductance regulator cftr gene in 1989, there has been significant interest in the possibility of gene therapy as a treatment for cf. Feb 15, 1999 gene therapy for the treatment of cystic fibrosis should be a natural. Cystic fibrosis cf is an insidious disease that slowly smothers the health and potential of too many young lives. The baby born with cf has normal lungs at birth, but evidence of inflammation and lung changes are present as early as 4 weeks of age. Therapeutic genes can be delivered to and expressed in human airways, but the number of cells expressing the.
Sep 29, 2004 gene therapy is currently being evaluated for a wide range of acute and chronic lung diseases including acute respiratory distress syndrome ards, cancer, asthma, emphysema and cystic fibrosis. Therefore, a large genomic construct spanning 300 kb from the 79. Gene therapy for cystic fibrosis horae gene therapy center. Prospects for gene therapy in cystic fibrosis archives of disease in. We funded the uk gene therapy consortium gtc to develop a gene therapy product with the potential to correct the faulty cystic fibrosis gene in the lungs. Advances in cell and genebased therapies for cystic fibrosis. As a result, patients suffer from blocked airways and bacterial infections. Challenges and strategies for cystic fibrosis lung gene therapy. The present invention comprises gene therapy for treating cystic fibrosiscf.
Cystic fibrosis centers for disease control and prevention. Cystic fibrosis cystic fibrosis is an inherited disease that causes thick, sticky mucus to build up in the lungs and digestive tract. Volume 120, issue 3, supplement, september 2001, pages 124s1s. Gene therapy is an alternative treatment for genetic lung disease, especially monogenic disorders such as cystic fibrosis. Cf pri marily affects the respiratory and digestive systems in children and young adults. Here we discuss the history of cf gene therapy, from the discovery of the cftr gene to current stateoftheart. In 1989, the gene causing cystic fibrosis cf was discovered. Cystic fibrosis cf is a recessive disease associated with loss of function mutations in the cf transmembrane conductance regulator cftr gene, which has a wellcharacterized gene product. Gene delivery systemsgene therapy vectors for cystic fibrosis. New gene therapy could treat cystic fibrosis with one dose. Cystic fibrosis patients are, in many cases, unrealistically pinning their hopes upon gene therapy which, as was pointed out in an editorial in thelancet, may have been oversold. Clinical trials have already been performed using cationic liposome and adenoviral based gene transfer systems, measuring the safety and efficacy of this. Ideally, future novel treatments such as gene therapy.
Gene therapy in cystic fibrosis archives of disease in. Cf is caused by mutations in the cystic fibrosis transmembrane conductance regulator cftr gene, which encodes a chloride and bicarbonate channel expressed in epithelial cells of the many organs affected in this disease. Alton ewfw, armstrong dk, ashby d, et al on behalf of the uk cystic fibrosis gene therapy consortium. Recent studies have identified the underlying molecular defect in cystic fibrosis cf. Cystic fibrosis transmembrane regulator replacement therapy cystic fibrosis transmembrane regulator pharmacotherapy stimulation of alternative chloride channels inhibition of sodium. Us5240846a gene therapy vector for cystic fibrosis. Cystic fibrosis is the lethal inherited disease that effects lungs pancreas sweat glands. Cystic fibrosis cf is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator cftr gene that encodes a campregulated anion channel. Cystic fibrosis is one of the most common genetic conditions in the world, and has always been at the forefront of gene therapy research.
Mutations in cftr lead to imbalanced water and ion movement across the airway epithelium, resulting in thickened mucus, chronic bacterial infection and inflammation, with progressive loss of pulmonary function. Status of gene therapy for cystic fibrosis lung disease. Pdf adenoassociated virus for cystic fibrosis gene therapy. Cystic fibrosis cf is an autosomal recessive disease caused by mutations of the cftr gene, which encodes a member of the adenosine triphosphate.
Gene therapy for cystic fibrosis lung disease sciencedaily. Pdf gene therapy is being developed as a novel treatment for cystic fibrosis cf, a condition that has hitherto been widelyresearched. Cystic fibrosis cf is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator cftr. Gene replacement therapy represents an interesting new approach for the treatment of cystic fibrosis cf lung disease. We funded the uk gene therapy consortium gtc to develop a gene therapy product with the potential to correct the faulty. Since the discovery of the gene encoding cystic fibrosis cf, there has been much excitement about the possibility of gene therapy, which has now reached the stage of phase i. Another option for treatment would be to give a person with cf the active form of the protein product that is scarce or missing. Researchers have demonstrated the efficacy of the technique in a mouse model of cystic fibrosis cf, and phase iii clinical trials have now begun. Frontiers gene therapy for cystic fibrosis lung disease. Cystic fibrosis is a genetic disease that causes mucus to build up in. A new partnership in the uk will develop a gene therapy for cystic fibrosis that could treat the disease with a single dose.
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