Sunday, July 26, 2009

Dawn if you are reading this...

I keep trying to respond to your email but it keeps getting bounced back to me!  Email me :)

Tuesday, July 21, 2009

Common cold virus efficiently delivers corrected gene to cystic fibrosis cells

Common cold virus efficiently delivers corrected gene to cystic fibrosis cells

CHAPEL HILL -- Scientists have worked for 20 years to perfect gene therapy for the treatment of cystic fibrosis, which causes the body to produce dehydrated, thicker-than-normal mucus that clogs the lungs and leads to life threatening infections.

Now University of North Carolina at Chapel Hill School of Medicine scientists have found what may be the most efficient way to deliver a corrected gene to lung cells collected from cystic fibrosis patients. They also showed that it may take this high level of efficiency for cystic fibrosis (CF) patients to see any benefit from gene therapy.

Using parainfluenza virus, one of the viruses that causes common colds, the UNC scientists found that delivery of a corrected version of the CFTR gene to 25 percent of cells grown in a tissue culture model that resembles the lining of the human airways was sufficient to restore normal function back to the tissue.

"This is the first demonstration in which we've been able to execute delivery in an efficient manner," said Ray Pickles, Ph.D., associate professor of microbiology and immunology at the UNC Cystic Fibrosis Research and Treatment Center. "When you consider that in past gene therapy studies, the targeting efficiency has been somewhere around 0.1 percent of cells, you can see this is a giant leap forward."

"We discovered that if you take a virus that has evolved to infect the human airways, and you engineer a normal CFTR gene into it, you can use this virus to correct all of the hallmark CF features in the model system that we used," Pickles said. For instance, the experiment improved the cells' ability to hydrate and transport mucus secretions.

The resulting paper is published in the July 21 issue of the journal PLoS Biology.

Now the researchers must work to ensure the safety of the delivery system. In a pleasant surprise, simply adding the CFTR gene to the virus significantly attenuated it, potentially reducing its ability to cause inflammation. But the scientists may need to alter the virus further.

"We haven't generated a vector that we can go out and give to patients now," Pickles said, "but these studies continue to convince us that a gene replacement therapy for CF patients will some day be available in the future."

In addition to Pickles, UNC co-authors are Liqun Zhang Ph.D, research associate, CF Center; Brian Button Ph.D., assistant professor, CF Center; Sherif E. Gabriel Ph.D., associate professor, pediatrics); Susan Burkett, research analyst, CF Center; Yu Yan, research specialist, CF Center; Yan Li Dang, research specialist, CF Center; Tristan McKay Ph.D., postdoctoral fellow, CF Center; and Richard C. Boucher M.D., Kenan Professor of Medicine, director, CF Center.

Other co-authors are April Mengos of the Mayo Clinic College of Medicine, as well as Mario H. Skiadopoulos, Ph.D., Leatrice N. Vogel and Peter L. Collins Ph.D., all of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

The research was funded by the National Institutes of Health and the Cystic Fibrosis Foundation.

Friday, July 17, 2009

New Drug with potential to treat both PA and B. Cepacia

Cystic Fibrosis - Liposomal Tobramycin Receives Second Orphan Drug Designation Within Weeks

Main Category: Cystic Fibrosis
Also Included In: Pharma Industry / Biotech Industry
Article Date: 17 Jul 2009 - 2:00 PDT

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An innovative treatment for infections of the respiratory tract in cystic fibrosis patients has received a second orphan drug designation in the US only weeks after a first designation was granted. The recent designation relates to Burkholderia cepacia pathogens that can cause lethal infections in cystic fibrosis patients. For Axentis Pharma AG of Zurich, Switzerland, both designations affirm the therapeutic potential of its product candidate Fluidosomes(TM)-tobramycin, whose unique microbiological profile sets it apart from other antibiotic formulations (including free tobramycin).

Axentis Pharma (Switzerland) announced that the Office of Orphan Products Development of the US Food and Drug Administration (FDA) has granted a second orphan drug designation to its lead product candidate Fluidosomes(TM)-tobramycin. This drug is a liposomal formulation of tobramycin and an innovative treatment for infections of the respiratory tract in patients with cystic fibrosis. Only three months ago, the FDA granted Fluidosomes(TM)-tobramycin orphan drug designation for the treatment of pulmonary infections caused by Pseudomonas aeruginosa. The newly granted second designation relates to pulmonary infections caused by Burkholderia cepacia (B. cepacia) pathogens.

Despite stringent infection control practices, B. cepacia infections still occur in cystic fibrosis patients and can lead to fatal sepsis. The cell envelopes of these especially virulent bacteria are impermeable to most antibiotics, which makes them particularly difficult to treat. Due to its unique mode of action, which allows the antibiotics to penetrate into the bacteria, Fluidosomes(TM)-tobramycin could become a particularly effective treatment for B. cepacia infections.

Prof. Dr. Miguel A Valvano, MD, Medical Advisor to Axentis Pharma, comments on the development: "Burkholderia cepacia is almost always multi-resistant to antibiotics and this, in conjunction with the poor prognosis of patients with B. cepacia infection, makes the treatment of these patients exceedingly complex. Tobramycin is in principle an effective antibiotic. The drug is however rather ineffective due to the impermeability of B. cepacia's cell envelope. In addition, B. cepacia - just like many other pathogens - has developed mechanisms to eliminate antibiotics once they have entered the cell. Fluidosomes(TM)-tobramycin seems to overcome these limitations by packing tobramycin into liposomes, which, by allowing effective penetration of the antibiotic into the bacterial cell, completely changes the microbiological profile of this antibiotic. Hence, Fluidosomes(TM)-tobramycin could be a totally new antibiotic formulation that addresses microbiological needs that no other antibiotic can."

What exactly happens when Fluidosomes(TM)-tobramycin encounters the bacterium is still not entirely clear, but pre-clinical data indicate a novel mode of action. Dr. Helmut Brunar, CEO of Axentis Pharma explains: "Once at the site of infection, tobramycin-containing liposomes seem to fuse with the cell membrane of the pathogen. In this way, the entire load of tobramycin contained in the Fluidosomes(TM) is released into the bacterial cell. Additionally, our data indicate that bacterial rescue mechanisms that pump tobramycin out of the cell are inhibited by the fusion process. The efficient delivery and maximum release of tobramycin into the bacterial cell together with inhibition of the clearance mechanism indicate that Fluidosomes(TM)-tobramycin has a highly efficient therapeutic effect."

About Axentis Pharma AG

Axentis Pharma is a respiratory specialty pharmaceutical company whose core competence is the combination of a fully patented, liposome-based drug delivery system with already established and well-characterized therapeutic agents. The company is using its platform delivery technology, named Fluidosomes(TM) technology, for the development of its lead product, an inhalable liposomal formulation of tobramycin. Axentis Pharma's lead product is designed to treat bacterial infections in the lungs.

About Fluidosomes(TM) technology

Axentis Pharma's Fluidosomes(TM) technology uses biocompatible lipids endogenous to the lung that are formulated into small liposomes. This nanocapsule platform offers wide-ranging potential for unmet medical needs, including chronic respiratory infections of the lung. In the case of Fluidosomes(TM)-tobramycin, the interaction between tobramycin and the microbial cell is triggered when the liposomes undergo a fusion process with the outer membrane of the bacterial cell wall. Tobramycin then penetrates into the inner cell compartment and triggers bacterial cell death.

Source: Axentis Pharma AG

Thursday, July 16, 2009

Cystic fibrosis treatments may have unseen long-term benefits

Cystic fibrosis treatments may have unseen long-term benefits

Cystic fibrosis medicines that help to break down mucus in the lungs may carry an unexpected long-term benefit, a study suggests

Cystic fibrosis medicines that help to break down mucus in the lungs may carry an unexpected long-term benefit, a study suggests.

The treatments not only help breathing in the short term - they may also make lung infections develop to be less harmful in the long run, research from the University of Edinburgh shows.

Scientists studied how bacteria which infect the lungs of cystic fibrosis patients gather nutrients from their surroundings. The work builds on the knowledge that most bacteria co-operate to scavenge what they need from their environment, but some bacteria do not actively hunt, instead stealing nutrients from neighbouring bacteria.

Scientists found that in a viscous environment, similar to thick mucus, the co-operating type of bacteria is most common. However, in a more liquid environment - similar to mucus having been broken down by medicine - the number of thieving bacteria increases, eventually outnumbering the scavenging type. In this environment, because the thieving bacteria are less adept at obtaining food, the bacterial growth slows down.

The results suggest that liquefying lung mucus would be expected to limit the impact of infection in cystic fibrosis.

Dr Rolf Kuemmerli, formerly a researcher at the University of Edinburgh, who led the study, said: "Treating cystic fibrosis patients with drugs that clear their lungs delivers short-term relief for the patient, but may have long-term health benefits too. We hope that our findings will underline the need for treatments that target mucus in the lungs."

Dr Freya Harrison of the University of Bath, who took part in the study, added: "Bacterial infections develop over time, and understanding how medical treatments affect this could be very important for managing long-term infections such as those found in cystic fibrosis."

Cystic fibrosis is an inherited condition that affects more than 8,000 people in the UK, according to the Cystic Fibrosis Trust. Thick mucus can clog the internal organs, especially the lungs and digestive system, making it hard to breathe and digest food.


The study, carried out by researchers at the Universities of Edinburgh, Oxford and Bath, was published in Proceedings of the Royal Society B. Work was supported by the Royal Society and the Leverhulme Trust.

Wednesday, July 1, 2009

Second/Third Opinions

Several people commented about second/third opinions, so I thought that I would globally update on that :) I contacted both UNC and Denver. The nurse at UNC is going to talk to the doctors there and see if we can get IR to look at Gess's last procedure. That seems like the most logical first step. The IR folks at UNC are very familiar with CF patients and bleeding and Gess had his first 7 embolizations done there. The doctors rock, the nurse coordinator is AMAZING. UNC is a great clinic!

I also contacted Denver and actually spoke with Dr. Nick (the adult clinic director) about the issue. He didn't seem especially optimistic that they would be able to do anything differently for Gess regarding the bleeding. In fact, he told me that embolizations are really only good as life-saving measures. He said that they could look at Gess's overall treatment plan, etc., but said that it was likely that they would recommend anything different. So...we aren't going to plan a trip to Denver just for a clinic visit at this point. We will probably see the docs there the next time we are in Colorado (Gess's family lives there) just for another set of eyes, but it doesn't sound promising for our immediate concern.

So, right now it is UNC. The nurse should get back to me next week and then we will go from there.