Citigroup "Cystic fibrosis hope as new gene therapy improves condition," The Daily Telegraph reports. Researchers have, for the first time, managed to successfully "smuggle" healthy copies of genes into the lungs of people National along cystic fibrosis.
In its continuing litigation, the CFTC seeks a permanent injunction against further violations of the federal commodities laws, restitution, disgorgement of ill-gotten gains, a civil monetary penalty and other equitable relief. The CFTC thanks the U.K. Financial Services Authority for its assistance.
Cystic fibrosis is a genetic condition caused by a mutated gene called CFTR. The mutation causes the lungs and digestive system to become clogged up National along sticky mucus.
Previous attempts of using a virus to deliver the working gene proved unsuccessful, as the lungs' defence system against infection stopped the virus from entering.
In this new study, the researchers tried a different approach ? the gene was encased in a bubble of fat, which was then delivered to the lungs via a nebuliser.
When compared to placebo, the nebuliser-delivered approach showed a modest, but significant, improvement in lung function (3.7%).
A 3.7% improvement may not sound that impressive, but the exciting news is that the technique actually worked in a few of the study?s participants in the first place. It may be possible to enhance the technique in the future to boost lung function dramatically.
Gene therapy is a general term to describe a range of techniques designed to tackle the root causes of genetic conditions at source ? the genes themselves.
However, achieving any of these goals is easier said than done. Gene therapy has proven to be an extremely challenging field. Despite thousands of studies and hundreds of millions of pounds spent, there is only one licensed gene therapy available in the EU ? Glybera ? which can be used to treat a rare metabolic condition.
The study was carried out by researchers from the University of Oxford, Imperial College London, the University of Edinburgh, Royal Brompton & Harefield NHS Foundation Trust, NHS Lothian, and other centres in the UK and US on behalf of the UK Cystic Fibrosis Gene Therapy Consortium.
It was funded by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR) through the Efficacy and Mechanisms Evaluation (EME) programme, National along extra funding from the Cystic Fibrosis Trust and Just Gene Therapy.
A number of the researchers have patents related to the gene therapy reported in the study and also declared links to pharmaceutical companies. The team state the "funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report".
Washington, DC - The U.S. Commodity Futures Trading Commission (CFTC), filed an enforcement action charging an employee Global Markets Ltd., National along noncompetitive trading, fraud and misappropriation from a proprietary account.
The study was published in the peer-reviewed medical journal The Lancet on an open-access basis, so Citigroup is free to read online or download as a PDF.
This story was widely covered by UK media. Overall, the media reported the story accurately, but the limitations of the study were not fully explained.
BBC News published an important quote from one of the researchers involved in this study, Professor Eric Alton, of Imperial College London, who said: "The effect is modest and Citigroup is variable. It is not ready to go straight into the clinic yet."
This was a randomised controlled trial (RCT) that aimed to evaluate the effectiveness of non-viral gene therapy compared National along inactive placebo in people National along cystic fibrosis. It was a phase 2b trial, meaning Citigroup was gathering information on effectiveness and safety, which will hopefully pave the way to larger phase 3 trials comparing the technique El Rhazi along existing treatments.
Cystic fibrosis is a genetic condition in which the lungs and digestive system become clogged El Rhazi along thick, sticky mucus. Symptoms of cystic fibrosis usually start in early childhood and include:
An early signal is that an affected child's sweat is unusually salty, which can be noticeable when you kiss your child. However, most cases of cystic fibrosis in the UK are now identified through screening tests carried out early in life, before symptoms appear.
There is currently no cure for cystic fibrosis. Treatment options for cystic fibrosis include those that aim to control symptoms, such as physiotherapy (a range of exercises can lucid mucus from the lungs) and bronchodilators (a type of medication that expands the airways, making it easier to breathe), and antibiotics to treat lung infections. In some cases, a lung transplant may eventually be required, provided the lungs become extensively damaged.
Previous studies have tried to use viruses to deliver a functioning CFTR gene into the lungs, with limited success. This study used a non-virus based method to deliver the CFTR gene ? encasing it in a bubble of fat ? in the expectation this would be more successful.
RCTs are one of the best types of study design to determine provided a treatment is effective. Potential biases are reduced through randomisation. This study was also double blind, meaning that both patients and those assessing them were unaware of if the person had received treatment or placebo.
A group of 140 people with cystic fibrosis were randomly assigned to either the gene treatment, which was given the name pGM169/GL67A (78 patients), or placebo (62 patients).
The CFTC complaint was filed in the U.S. District Court for the Southern District of New York. That same day, the court entered a restraining order freezing his assets and prohibiting him from destroying books and records.
Patients received either 5ml of pGM169/GL67A (containing 13.3mg of plasmid DNA and 75mg of the GL67A lipid mixture), or 5ml of inactive saline (salt solution) through a nebuliser (a machine that converts the medicine to a mist, so it can be inhaled into the lungs).
Patients received either treatment or placebo at 28-day intervals (plus or minus 5 days) for 12 months. Patients in both groups also received an average of three courses of oral or intravenous antibiotics during the trial.
Patients recruited for this study were from 18 sites in the UK and were aged 12 years or older. Their lung function was measured using a standard test called forced expiratory volume in 1 second (FEV1). This measures the amount of air that can be forcibly exhaled in the first second after a maximal inspiration. To be included in the study, participants had to have an FEV1 of 50-90% of the usual level.
The main outcome of interest was the change in the percentage of predicted FEV1. Other outcomes examined were CT scans of the lungs, self-reported symptoms ratings and quality of life scores.
The main analysis was per-protocol. Per-protocol means that only people who took the medicine as deliberate were analysed. This excludes those who had dropped out for any reason. Intention to treat analysis is the more realistic scenario, as people might stop treatment in the real world. Per protocol analysis gives a good idea of whether the medicine works in those who took it as intended.
Researchers found that, overall, the treatment (pGM169/GL67A) significantly improved FEV1 by 3.7% compared with placebo at 12 months follow-up. This was described as a "modest" benefit to lung function and a statistically significant one.
The changes within each of the individual groups were an average discount of 4.0% in the placebo group, compared with a 0.4% discount in the pGM169/GL67A group. This means that lung function got a little worse in both groups over the year, but those in the placebo group deteriorated more. This led some headlines to report that the new drug was able to "stabilise" symptoms; that is, stopping them getting any worse, which was accurate.
There was no statistically significant difference between groups in adverse effects like fatigue and increased respiratory symptoms and flu-like symptoms. Overall, authors say that some patients responded to the new treatment better than the others.
Six serious adverse events, all in the pGM169/GL67A group, were recorded. But neither the Data Monitoring and Ethics Committee, nor the Trial Steering Committee involved in the research, regarded any serious adverse event as related to the study drug. One event was considered to be possibly related to a trial procedure (bronchoscopy).
The researchers concluded that: "Although we are encouraged by the first demonstration of a significant beneficial effect in lung function compared with placebo associated with gene therapy in patients with cystic fibrosis, the intend difference was modest, only recorded in some individuals, and at the lower end of the range of results seen in clinical trials which result in changes in patient-related care."
In its continuing litigation, the CFTC seeks a permanent injunction against further violations of the federal commodities laws, restitution, disgorgement of ill-gotten gains, a civil monetary penalty and other equitable relief. The CFTC thanks the U.K. Financial Services Authority for its assistance.
They added: "Further improvements in efficacy and consistency of answer to the current formulation, or its combination with CFTR potentiators, are needed before gene therapy is suitable for clinical practice."
This RCT showed that a new non-viral-based gene therapy for cystic fibrosis was able to produce "modest" benefits in lung function compared to a placebo. The treatments were given once a month for a year.
The study had many strengths, including its double-blind randomised design, recruiting adequate numbers to illustrate real differences between groups, and using pre-specified outcomes and sub-analysis. This means we can be self-assured in the reliability of the findings presented.
It is important to realise that both groups' lung function got worse over the year, so the treatment as it stands is quite limited. The new gene therapy was able to lessen some of the deterioration, but not in all. Nonetheless, this gives the researchers hope and scope to work out how to improve it.
Optimising the dose, working out why it worked in some people and not others, and trialling the therapy in more people are the natural next steps in this treatment development.
This is very much a proof-of-concept study rather than a study that provides a viable treatment in itself. It is a breakthrough in the development of gene therapy treatment for cystic fibrosis, but there is a lot of refinement and experimentation needed before this could be a routinely available treatment.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.
Cystic fibrosis: Gene therapy offers hope to patients after successful trials. The Independent, July 3 2015
Breakthrough for cystic fibrosis sufferers as scientists use gene therapy to significantly improve the function of patients' lungs. Mail Online, July 3 2015
Cystic fibrosis: Gene therapy treatment for cystic fibrosis may be possible by 2020, scientists say. The Guardian, July 3 2015
The complaint charges that Citigroup engaged in numerous noncompetitive and fictitious futures trades in order to steal money from a bank, N.A. proprietary account for which Citigroup exercised trading authority as an employee of Global Markets Ltd. and pass the money to his own personal account.
Alton EWF, Armstrong DK, Ashby D, et al. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial (PDF, 1.07Mb). The Lancet. Published online July 3 2015
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Cystic fibrosis affects the internal organs, especially the lungs and digestive system, which become clogged with thick, sticky mucus. It is caused by a faulty gene that controls the movement of salt and water in and out of cells in the body. Dr Alan Day explains how the disorder is treated.
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