Enlightening Conversation About Vertex Results

I thought it would be good to share a conversation I had today with a momma in the community that wasn't exactly pleased with my thoughts/comments/commentary on the Vertex announcement yesterday. Many of you may feel the same way...

"I am upset at the comments you made yesterday and the one today."

What specifically upset you? (see paragraph towards the end of this post for her response to this question)

"I am surprised that you would post things that could upset parents and other CF'ERS that have new hope. I understand that you have strong feelings and emotions about this combo and they are rightfully yours to have."

Right. And I'll always be honest, even if that means a few feathers are ruffled or I have some push back. And if posting something accurate and truthful on FB takes away the hope of some, I am sorry. With that said, I also included parts in my statement that would support the hope felt like "There are also people who blew the doors off of old PFT results!!!!!" or "I'm not saying that this is not good news." or "And I've always been consistent in saying that we do not need to see positive numbers for it to be a success. Remaining steady would be a BIG WIN for the CF community."

"However, the post yesterday was used by others to continue to be hateful to many in the community."

I cannot control what others do, and I will never censor myself based upon the possibility of others using my words out of context. That would not be authentic and I certainly won't put on a false facade - with what I say or what I don't.

"It may not be what you intended but it came across as you being mad that you were not able to get them at a time when you were younger."

Honestly, I have no clue how that came across to you in what I said. Do you think I would volunteer 1000's of hours a year in the CF community, if I were mad or bitter in any way at the opportunities afforded to the younger generation? Does that sound like a guy who thinks "life isn't fair"? I thought that was pretty clear when I said, "My biggest goal, and frankly why I got so involved with the CF community, is to make the life experience of the next generation of CFers, and the generation after that, better than my own. I don't want to see the CF patients of the 90's, 00's and 10's experience the same struggles as I did, a patient of the 80's."

"I have always respected you and seen you as such a godly man. (I even spoke of how you were such to my mother yesterday when everyone else was posting hateful comments)."

I'm certainly happy to hear that you think (or thought?) of me in that way. I do my best to show God's love through my approach and interaction with others, and unfortunately, I'm pretty sure I fail everyday. I can assure you if I served a God that wasn't gracious, I'd be screwed.

"To see your post after saying these things was disappointing. I hope that you see that your posts can be hurtful and truly upsetting to some."

Again, I am sorry if anyone was hurt by my commentary yesterday. This was in direct response to seeing statements like "I'll finally be able to breathe again" or "This may be my last hospital stay ever!!" or "We'll basically be cured." or "I can't wait to take those pills and for this to all be over!". We still have a long way to go. As it stands right now, the combo drugs will not support the statements above for the majority of people with CF. Less exacerbations? Probably. Less frequent hospital stays? Probably. Maintain lung function for longer? Probably. Cure? No. No hospital stays ever again? Probably not. No more treatments? Probably not.

"You have been given a wonderful platform to be such a strong witness for the Lord. I am always so thankful for your standing up for what is right and true."

I will continue to do so.

"Please know that this is not intended to be mean, just expressing how this has made one Christian woman feel."

Not a problem. I didn't think it was mean at all. It's hard to articulate feelings through an online medium such as FB. Expressing oneself, and having different feelings towards the same object/result/person is what personal expression is all about.

"I want this combo to give you decades more to work for the Lord and be with your family as much as I want it for my little girl."

Amen. I want the combo to work for your little girl with every fiber of my being. I would gladly give up any potential decades I have left to see that happen.

"On a side note, the lawsuit against Vertex being brought forward by the state of MA makes me question the validity considering their health care system. Just a thought."

The lawsuit is about people purchasing the stock based on "grossly overstated" results by said company and then losing 100's of thousands of dollars when that information was redacted...all the while executives of said company potentially made 100's of thousands of dollars by selling a portion of their shares before the results were corrected.

"I think the most upsetting part was saying I hate to be that guy type of comment. It kind of starts you off with a negative attitude. I did not see the comments from people that you mentioned. I do not think this is the end of treatments or anything for my daughter. But I do think it could keep her where she is until something better comes along which is more than I've had before. I know that most parents feel hope but know this is not a cure. For those of us who have a realistic view of the combo, the post was like someone coming into the first glimmer of hope we've had and screaming "just kidding!". Because we look up to you so much....I don't think you are bitter and that's why I even said something because it seemed out of character. I know you can't control what others do; however, if you had read what some were saying you might have held off on.that comment for a few days. It's ugly out there...and it just gets worse. It's hard for a parent of a child with CF that deals so much to see the negativity we've seen from this announcement. There are so many that have been so hateful about this not helping them that they don't want anyone else to have hope. It seems like such a miserable life for them and it's hard to understand. Your posts may not have upset me on another day but after dealing with all the negativity it was hard to see yours. I do not look at you differently now. I just wanted to let you know how it is from a mommy's view right now. There was such excitement for Kalydeco and we can't have the same joy that's all we want. I know you want that too. Thanks for responding! And I want address the other comments on the lost because I don't feel it's okay to stir the pot. But feel free to share this without my name." 

Totally understand where you are coming from [withheld]. I can see why this may have felt like I was piling on. It was never intended to be that way. I was trying to provide some history and context to a community that has felt let down many times in the past based on announcements like this only to discover it's not what they thought it would be. I'm sure I could have worded it better or, as you suggested, wait for the flames to die down a bit before throwing some gasoline on them.

On a side note: Did you know that I am currently on the drug and I think it helps? Maybe that would have been beneficial for me to say?

"I had no idea. I am thankful you are and are doing well on it! I hope it keeps you healthy and at home with your family more so than not! It would probably put out the fire if you said that ;)"

Haha, maybe I'll mention it then. I didn't see PFT improvement, but I think it gave me the ability to fight off infection quicker and I have remained stable for longer periods of time.

Proceed with Caution - Vertex's Big News

For those of you who haven't heard, Vertex announced the results of it's big Phase III combo drug that may cover roughly 50% of the community. You can read the press release here.

I'm so pumped to see the joy and hope exhibited by so many in the CF community today. I hate to "be that guy", but I did want to throw out a bit of context and history to be sure that we are all managing our expectations:

1. The Phase 3 study showed an average increase in lung function of 3% Context: Cayston showed a 2% increase in it's Phase 3 head-to-head study against TIS.

2. The results have not been completely vetted by those outside of Vertex. Context: This is the same company that is now being sued for "grossly overstated" results in the Phase 2 trial of the combo drugs - http://ow.ly/yp7L2

3. About 46 people dropped out of the Phase 3 study because of complications. Context: Extrapolate this to the potential users of this combo, and you'd have around 1400 people with DDF508 who still wouldn't benefit from this drug. You'd also have to include those who saw no benefit but elected to stay in the trial. (NOTE: There are also people who blew the doors off of old PFT results!!!!!)

I could go on, but I'm feeling like Captain Buzzkill. I just see a lot of celebrating without facts (or misinformation) and want peeps out there to understand that we have a long way to go for the next generation of CFers. With that said, if this drug has the potential to in essence halt the decline in lung function at an early age, I'd cut off my left arm if that meant that everyone had access to it.

#captainbuzzkill

Added after reading feedback: Yes, celebrate!! Any move towards a better life experience while managing cystic fibrosis is a win. I'm not saying that this is not good news. Selfishly, anything that could possibly extend my life even a minute with my wife and daughter, is something worth being excited about. My biggest goal, and frankly why I got so involved with the CF community, is to make the life experience of the next generation of CFers, and the generation after that, better than my own. I don't want to see the CF patients of the 90's, 00's and 10's experience the same struggles as I did, a patient of the 80's. Progress doesn't only come in the form of a pill, but I'll sure as heck take one if/when it does!

And I've always been consistent in saying that we do not need to see positive numbers for it to be a success. Remaining steady would be a BIG WIN for the CF community. Shoot, not having to work so hard to maintain what I currently have is something I'd pay good money for :)

(I took this from my FB page as I know many of you are not friends of mine on there yet you read this blog. I'd love to hear your thoughts)

Limited Exercise Research

I thought this was a very interesting article highlighting the limited research on exercise. I've highlighted the biggest take-aways if you don't have the time to read the whole thing.

“A lot of physiologists come into the discipline because they fundamentally like exercise,” Martin Gibala, an exercise physiologist at McMaster University in Ontario, told me. “But you learn very quickly that there’s not a lot of research money out there to fund applied studies.” On matters as simple as how many sets and reps best promote muscle growth, Mr. Gibala explained, “We can’t nail down the answer.”
Even if the funding were there, Mr. Gibala says, “That’s not state-of-the-art research that you’re going to publish in the best journals and advance your career.” Instead, he says, physiologists study questions of basic science, “like the molecular signaling proteins that regulate skeletal muscle adaptation.”

I also thought of the CF community and what we're trying to do in promoting patient-centered or patient-driven research when I read this...

The human body is an adaptation machine. If you force it to do something a little harder than it has had to do recently, it will respond — afterward, while you rest — by changing enough to be able to do that new hard task more comfortably next time. This is known as the progressive overload principle. All athletic training involves manipulating that principle through small, steady increases in weight, speed, distance or whatever.
So if your own exercise routine hasn’t brought the changes you’d like, and if you share my vulnerability to anything that sounds like science, remember: If you pay too much attention to stories about exercise research, you’ll stay bewildered; but if you trust the practical knowledge of established athletic cultures, and keep your eye on the progressive overload principle, you will reach a state of clarity.

I think we all see people in the CF community that are doing the things and making the choices that work for them. In some cases, there is a large cohort of the CF community that has bought into a certain lifestyle or treatment or "culture" that seems to be having positive effects. I look forward to identifying those a doing what we can to promote research around those areas.

If you have any comments, I'd love to hear them.

http://www.nytimes.com/2014/05/25/opinion/sunday/fitness-crazed.html?_r=1

Vitamin D Levels Tied to Lung Health

Serum vitamin D levels had a significant positive correlation with pulmonary function, most prominently in patients with a history of tuberculosis (TB), data from a large cross-sectional study showed.

...

In the subgroup of patients with a history of pulmonary tuberculosis, the absolute difference in FEV₁ by 25-OHD level was four times greater than the difference in the overall population, they wrote in the Journal of Clinical Endocrinology & Metabolism.

...

"The precise mechanism for this phenomenon remains unknown, but it has been suggested that vitamin D accelerates recovery from infection by enhancing innate immunity via upregulation of antimicrobial peptides," they added.

Observational studies of vitamin D and respiratory function have yielded mixed results. Clinical trials of vitamin D supplements as prophylaxis against respiratory disease also failed to demonstrate a definitive association, the authors said.

...

Comparing the top and bottom quartiles of 25-OHD, the authors found a difference of 229 mL for FEV₁ in the subgroup of participants with a history of pulmonary TB (P<0 .01="" p="">

The study had some limitations, namely that it was cross-sectional so reverse causality could not be ruled out. Also, the overall low 25-OHD levels in the participants limited the authors' ability to adequately estimate optimal vitamin D levels for lung function. Finally, data on sun exposure and dietary or supplementary vitamin D intake were not available.

To read the full article on Medpage Today, click here.

Inhaled Anti-Pseudomonal Drugs Promising in Cystic Fibrosis Patients

NEW YORK (Reuters Health) Dec 12 - Fosfomycin/tobramycin for inhalation (FTI) is a promising treatment for cystic fibrosis patients with chronic Pseudomonas aeruginosa airway infection and reduced lung function, researchers say.

Their phase II safety/efficacy study tested 28 days of FTI against placebo, immediately following 28 days of inhalation therapy with aztreonam.

Such continuous therapy is not typical. As the authors point out, "a 28-days 'on' and 28-days 'off' dosing schedule is used for inhaled antibiotics that are currently approved in the U.S. for airway P. aeruginosa in cystic fibrosis patients.

But the rationale for the "off" period is being questioned because of changing microbiological profiles and the increasing use of two or more inhaled antibiotics in rotation, they wrote online November 17 in the American Journal of Respiratory and Critical Care Medicine.

Both FTI and the aztreonam inhalation solution are being developed by Gilead Sciences, which sponsored the current trial.

Altogether researchers enrolled 119 patients (average age, 32 years) with a mean forced expiratory volume in one second (FEV1) of 49% predicted at screening.

After the 28-day open-label course of inhaled aztreonam three times daily, patients were randomly allocated to twice-daily FTI (60/40 mg or 80/20 mg) or placebo, for another 28 days.

With aztreonam, the mean improvement in FEV1 predicted was 7.0%. This improvement was maintained with FTI, whereas lung function in placebo-treated patients declined toward pre-aztreonam levels. The treatment effect favoring FTI 160/40 mg was 6.2% (p=0.002) and 7.5% favoring FTI 80/20 mg (p<0.001).

In addition, the researchers found reductions in mean P. aeruginosa sputum density in the FTI 80/20 group versus placebo (p=0.01).

FTI "was also effective against methicillin-resistant Staph aureus, for which there are relative fewer drugs," first author Dr. Bruce Trapnell, of University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Ohio, told Reuters Health.

He and his colleagues found that in 13 of 63 patients co-infected with S. aureus and P. aeruginosa, S. aureus could not be cultured from the end of the FTI treatment period (day 28) through the end of follow-up on day 56.

"However, the study was not set up or powered to evaluate this outcome," Dr. Trapnell cautioned. "The data should be considered supportive, but further studies are needed."

Fosfomycin is a phosphonic acid antibiotic active against gram-positive, gram-negative, and anaerobic bacteria. Tobramycin is an aminoglycoside with gram-negative activity.

"Adverse events, primarily cough," were noted, the authors say. Respiratory events, including dyspnea and wheeze, were less common with FTI 80/20 than FTI 160/40. All respiratory events were mild or moderate in severity, and there were no clinically significant changes in laboratory values.

Along with sponsorship by Gilead Sciences, Inc., the study was supported by grants from the FDA and the NIH General Clinical Research Center.

SOURCE: http://bit.ly/vjcVCR

Original article: http://www.medscape.com/viewarticle/755291?src=nl_topic

Eastern European CF Statistics

Call for European Cystic Fibrosis healthcare gap to be closed

A healthcare gap amounting to a ‘death sentence’ forCystic Fibrosis (CF) children born in Eastern Europe must be closed say researchers from the EuroCareCF Coordination Action for Cystic Fibrosis. A new study led by the University of Dundee and published today in The Lancet, has found that CF patients in Eastern European countries die far younger than in other, wealthier, EU countries.

EuroCareCF, led by Dr David Sheppard of the University of Bristol, provided a forum for groups from all over Europe to collaborate to improve the quality of life and life expectancy of individuals with CF. As part of this collaboration, Dr Anil Mehta of the University of Dundee led a team from 35 countries that examined outcomes for almost 30,000 CF sufferers born in long-standing European Union member states compared to those born in countries who joined after expansion in 2003. The resulting paper shows that despite similar population sizes and underlying gene frequencies for CF, the numbers of CF-affected children were lower in post-expansion EU member states. Dr Mehta says this disparity can most likely be explained by the tragic fact that a lack of healthcare facilities in new member states means that the majority of children born with CF in these countries will die in very early childhood, a situation not encountered in the wealthier EU countries for many decades. “We know that this disease occurs randomly in about 1 in 4,000 children born to healthy parents across the EU,” he said. “Despite this, the team encountered many fewer people with CF in poorer countries. CF patients there die far younger than in long standing EU countries.”

Nick Fahy, head of the health information unit in the Health and Consumers Directorate General at the European Commission, said, “Knowledge is key to improving health in Europe. For these rare diseases, there are so few centres of expertise that only by working together across the EU can we enable all citizens to have access to the best possible care. “This European cooperation also shows member states how they compare to best practice in Europe for different conditions, so that every health system can prioritise their resources to meet the needs of their patients."

Cystic fibrosis is an inherited chronic disease that affects many organs, particularly the lungs and digestive system. CF patients carry a defective gene that disrupts the transport of salt across cell borders. As a result, the body produces thick mucus that blocks ducts and tubes. Blockage of air passageways causes chronic cough and lung infection; blockage of the pancreasprevents enzyme delivery to the intestine to break down food; and blockage in the intestine prevents food absorption. Countries in Western Europe have committed significant resources to making the necessary treatment available to CF sufferers, helping them to live longer and fuller lives.

Read the rest of this article by clicking here or going to http://www.medicalnewsbase.com/medical-conditions/call-for-european-cystic-fibrosis-healthcare-gap-to-be-closed/

Discovery May Lead To New Cystic Fibrosis Treatments

PR Log (Press Release) – Mar 11, 2010 – Discovery may lead to new cystic fibrosis treatments

A new discovery may give hope to the thousands of cystic fibrosis sufferers around the world.

According to a research team from the University of California, San Diego School of Medicine, they have identified a defective signalling pathway which increases the severity of cystic fibrosis, a condition which affects one in 2,400 people in the UK, and of which four per cent of the population are carriers.

In the report, published in the February 14th edition of the journal Nature Medicine, lead investigator Dr Gregory Harmon and study supervisor Dr Christopher Glass, professor of cellular and molecular medicine at the facility, say that the discovery may be able to significantly reduce symptoms in sufferers.

The specialists revealed that defective signalling for a protein called the peroxisome proliferator-activated receptor-y (PPAR-y) accounts for a portion of disease symptoms in cystic fibrosis, and that the correction of the defective pathway reduces symptoms of the disease in mice.

Dr Harmon pointed out that cystic fibrosis results from a genetic mutation in a membrane pore that facilitates the transport of chloride and bicarbonate electrolytes from inside the cell to the spaces outside the cell.

He added: "Loss of the cystic fibrosis pore channel results in inflammation and mucus accumulation. It also results in dehydration of the cell surfaces that make up the lining spaces inside the lungs and other affected organs, such as the intestinal tract."

Dr Harmon revealed that the fact a drug may be able to activate bicarbonate transport without affecting chloride transport is what could result in an improvement in the disease.

"The finding of the reduced PPAR-y activating prostaglandin in cystic fibrosis is exciting since it could serve as a marker to identify which patients might benefit from treatment," the expert concluded.

find original article at http://www.prlog.org/10570893-discovery-may-lead-to-new-cystic-fibrosis-treatments.html

Exciting Article About Drug Delivery

Beating the cystic fibrosis barrier

Biodegradable nanoparticles capable of penetrating the mucus barrier in the lungs and gut of cystic fibrosis (CF) sufferers have been developed by researchers at John Hopkins University, led by Justin Hanes, professor of chemical and biomolecular engineering.

“Cystic fibrosis mucus is notoriously thick and sticky, and represents a huge barrier to aerosolised drug delivery,” said Pamela Zeitlin, CF expert and professor of paediatrics, who collaborated on the study. “Nanoparticles were engineered to travel through cystic fibrosis mucus at a much greater velocity than ever before, thereby improving drug delivery,” she said.

The nanoparticles comprise of two parts made of molecules regularly used in existing medications. An inner core of polysebacic acid (PSA) traps therapeutic agents inside while a dense outer coating of polyethylene glycol (PEG) molecules allows the particle to move through the mucus by preventing it from reacting with proteins.

Hanes previously demonstrated that latex coated with PEG could slip past mucus coatings, but because the body could not break it down into harmless components it was impractical. “The major advance here is that we were able to make biodegradable nanoparticles that can rapidly penetrate thick and sticky mucus secretions and that these particles can transport a wide range of therapeutic molecules,” said Hanes.

The nanoparticles have potential applications treating lung and cervical cancers, and inflammation of the sinuses, eyes, lungs and gastrointestinal tract where mucus is produced to protect sensitive areas, said Benjamin C Tang, lead author and postdoctoral fellow in the department of chemical and biomolecular engineering. Zeitlin concludes: “This work is critically important to moving forward with the next generation of small molecule and gene-based therapies.”

Read the full article here: http://www.labnews.co.uk/laboratory_article.php/5285/2/beating-the-cystic-fibrosis-barrier

Thankful for New Drugs!!!

This Thankful Thursday is a pretty easy one! I'm so thankful for the new drug just approved by our FDA :) I've heard nothing but great things about this drug from fellow cysters and fibros and I really can't wait to try it out myself. Make sure to call your clinic ASAP to see if this is a drug that can help you and one that you can get on sooner rather than later.

The drug by the way is Cayston, also known as AZLI. Think of it as another TOBI type of drug that can be done during your off month of TOBI or can be done instead of TOBI all together. It has to be taken three times a day, but the great part is, the treatment takes 2 to 3 minutes!!!

Bring it on!

Gilead Sciences, Inc. today announced that the U.S. Food and Drug Administration (FDA) has granted marketing approval for Cayston(R) (aztreonam for inhalation solution) as a treatment to improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa (P. aeruginosa). Cayston's safety and efficacy have not been established in pediatric patients below the age of 7, patients with forced expiratory volume in one second (FEV1) of less than 25 percent or greater than 75 percent predicted, or patients colonized with Burkholderia cepacia.

Cayston is administered at a dose of 75 mg three times daily over a 28-day period and is delivered via the Altera(R) Nebulizer System, a portable, drug-specific delivery device using the eFlow(R) Technology Platform, developed by PARI Pharma GmbH. PARI Pharma also contributed to the development of Cayston's drug formulation for delivery with the Altera Nebulizer System. Cayston will be available in the United States by the end of next week through certain specialty pharmacies.

"All of us at Gilead extend our thanks to the investigators and to the people with cystic fibrosis who took part in the Cayston clinical trials," said Norbert Bischofberger, PhD, Gilead's Executive Vice President, Research and Development and Chief Scientific Officer. "We look forward to making Cayston available to the cystic fibrosis community as soon as possible."

CF is a chronic, debilitating genetic condition that affects the respiratory and digestive systems of approximately 70,000 people worldwide, including 30,000 people in the United States. Chronic respiratory tract infection with P. aeruginosa contributes to the decline in pulmonary function, which is often associated with morbidity and mortality among CF patients.

"Since its founding in the 1950s, the Cystic Fibrosis Foundation has worked to advance the care and treatment of cystic fibrosis and we are pleased with the progress to date," said Robert J. Beall, PhD, President and Chief Executive Officer, Cystic Fibrosis Foundation. "However, a significant need for new treatments remains for people with cystic fibrosis, particularly for those with chronic pseudomonal infection. As the first new inhaled antibiotic approved for use in cystic fibrosis in more than a decade, Cayston therefore represents an important therapeutic option in the care of patients with cystic fibrosis."

Cayston received conditional marketing authorizations in the European Union and Canada in September 2009 and was approved in Australia in January 2010. Applications for marketing approval of Cayston are currently pending in Switzerland and Turkey.

Reimbursement and Access to Care

Gilead also announced today the establishment of a program designed to minimize barriers to access for Cayston for uninsured, privately insured and government-insured people with cystic fibrosis.

Additionally, Gilead is launching the Cayston(R) Access Program, a call center developed with Cystic Fibrosis Foundation Pharmacy, LLC, a wholly owned subsidiary of the Cystic Fibrosis Foundation. The program will assist people with cystic fibrosis and members of their care team with insurance verification, referral to participating specialty pharmacies, claims support and co-pay assistance. For information about the Cayston Access Program, call 1-877-7CAYSTON (877-722-9786) or visit www.cayston.com.

About Cayston

Cayston (aztreonam for inhalation solution) 75 mg is an inhaled antibiotic for patients with cystic fibrosis who have P. aeruginosa. Aztreonam has potent in vitro activity against gram-negative aerobic pathogens including P. aeruginosa. Cayston contains aztreonam formulated with lysine, a proprietary formulation of aztreonam developed specifically for inhalation. Aztreonam formulated with arginine has previously been approved by FDA for intravenous administration.

Cayston is administered three times a day for a 28-day course, followed by 28 days off of Cayston therapy. Cayston is administered by inhalation and should only be used with an Altera Nebulizer System. Patients should use a bronchodilator before administration of Cayston.

Article from Business Wire. February 22, 2010. To read the full article please click here.

Drug Improved Survival in Mice With Cystic Fibrosis

It may only be mice, but it's a start....

In the search for new treatments for cystic fibrosis, U.S. researchers have identified a defective signaling pathway that contributes to the severity of the inherited lung disease.

Cystic fibrosis causes thick, sticky mucus to build up in the lungs and digestive tract, and is one of the most common potentially lethal genetic diseases in children and young adults.

In the new study, the researchers found that correcting the defective signaling pathway for a protein called peroxisome proliferator-activated receptor-y (PPAR-y) reduced cystic fibrosis symptoms in mice.

"Cystic fibrosis results from a genetic mutation in a channel, or membrane pore, that facilitates the transport of chloride and bicarbonate electrolytes from inside the cell to the spaces outside the cell," lead investigator Dr. Gregory Harmon, of the University of California, San Diego School of Medicine, said in a news release from the school.

"Loss of the cystic fibrosis pore channel results in inflammation and mucus accumulation. It also results in dehydration of the cell surfaces that make up the lining spaces inside the lungs and other affected organs, such as the intestinal tract," he explained.

Working with cells from mice and human cell lines from cystic fibrosis patients, Harmon and his colleagues determined that multiple genes affected by PPAR-y were reduced in cystic fibrosis.

The researchers then treated mice with cystic fibrosis with the drug rosiglitazone (a drug that binds and activates PPAR-y) and found that gene expression was largely normalized and survival improved. Among the other findings:

• Drug treatment also corrected part of the inflammatory process associated with cystic fibrosis.
• Deleting PPAR-y in the intestine of mice worsened cystic fibrosis.
• Activating PPAR-y can increase bicarbonate production in intestinal tissue by increasing the activity of bicarbonate-producing enzymes called carbonic anhydrases.

"For the first time, we are able to use a drug that activates bicarbonate transport without affecting chloride transport, and see improvement in the disease," Harmon said.

The findings, published in the Feb. 14 issue of Nature Medicine, may lead to new treatments for cystic fibrosis.

Find original article at http://www.palmbeachpost.com/health/drug-improved-survival-in-mice-with-cystic-fibrosis-253691.html

New Drug Class Offers Hope Against "Superbugs"

This is very new discovery, but exciting to hear nonetheless!! For full article click here.

LONDON, Feb 18 (Reuters) - Swiss scientists have found a new class of antibiotics, offering drug developers a fresh weapon in the fight against multi-drug resistant bacteria or "superbugs".

Researchers from a privately held Swiss biotech company Polyphor and the University of Zurich said the potential medicines are effective against a type of bacteria known as "gram-negative", and offer hope for new treatments for serious and often life-threatening infections.

The antibiotics work by deactivating a protein vital for the formation of the bacteria's outer cell membrane.

Polyphor's chief financial officer said the firm was in talks with pharmaceutical firms about possible licensing deals on the most advanced drug candidate, called POL7080, which selectively kills the dangerous pseudomonas aeruginosa, a common bacteria that can cause lung infections.

"There is a big need for new antibiotics that can overcome rising resistance," Michael Altorfer told Reuters. "And if you look back in history, finding a new class of antibiotics is an event that probably happens about every 20 years."

Until recently, antibiotics have been viewed by drugmakers as a low-growth area but the emergence of superbugs has rekindled interest in the field.

A study published in the journal Science found that POL7080 was able to target and deactivate an essential protein of the pseudomonas bacteria, killing the bug.

A report in December found that gram-negative bacteria account for around 63 percent of infections in hospital intensive care units. Experts commenting on that study said they feared resistance among gram-negative bugs was rising while the number of medicines to treat them was shrinking. [ID:nN01516996]

Drug-resistant bacteria kill about 25,000 people a year in Europe and about 19,000 in the United States.

Altorfer said Polyphor is planning to start Phase I clinical trials in healthy volunteers in the second quarter of this year and had begun out-licensing negotiations with potential pharma partners. He declined to name any of the firms in talks.

Pseudomonas aeruginosa is a particular problem in hospital acquired infections and in patients with cystic fibrosis, whose lungs and digestive systems become clogged with a thick, sticky mucous.

Altorfer said he was keen not to raise hope, but the drug could potentially be made in an inhalable form to help cystic fibrosis patients, of which there are around 70,000 worldwide.

"But there are other indications that could come first, such as hospital acquired infections," he said.

Full article can be found at http://www.reuters.com/article/idUSLDE61G0OX20100218

Forced Indoor Air Ionization to Treat Cystic Fibrosis

I ran across this article the other day and I found it interesting so I thought I would share:

FORCED INDOOR AIR IONIZATION BY SALT SUBLIMATION MAY IMPROVE RESPIRATORY SYMPTOMS IN CYSTIC FIBROSIS

Forced ionization of indoor air by salt sublimation may improve respiratory symptoms in cystic fibrosis (CF), said a researcher in a presentation at the 24th European Cystic Fibrosis conference in Vienna, Austria.

The use of speleotherapy in many Central and Eastern European countries is well spread and well-known and in these countries doctors recommend this therapy to their patients.

The term speleotherapy comes from the Greek ‘speleo’ that means ‘cave’ – the therapy in a salt mine. Many, many people with all kinds of respiratory diseases use this therapy as a complementary or alternative therapy to the classical drug therapy and find great relief.

Being very effective but in the same time costly by having fixed location and the treatment implying multiple sessions, this physical therapy has been practiced in Balkans for over 150 years.

In an effort to find a way to use this therapy at home, a Romanian chemist engineer have researched and developed a device that is able to simulate the salt mine micro-environment in the comfort of your home. He have analyzed the air composition in a salt mine and found the way to grow salt micro particles as those found in a salt mine, using only natural mineral halite salt crystals formed in the Middle Miocene era from the salt mine.

All the research work was followed by clinical studies at different clinics in Romania. Now, the device uses forced indoor air ionization by salt sublimation and give so much relief in many respiratory conditions.

One of the clinical studies that have been done is regarding the effect of Salin device in patients with cystic fibrosis. Doctor Ioan Popa and his colleagues from a paediatric clinic in Buzau, Romania, investigated 18 patients with their age between 3 and 17 years old, with mild to severe cystic fibrosis.

This study has been realized within a 6 months interval on the two lots that were created. Seventy percent were diagnosed as having mild cystic fibrosis and thirty percent were severe. The two lots were created based on the stage of the diseases, their FEV1, colonisation with Pseudomonas aeruginosa and/or Staphylococcus aureus and other respiratory conditions.

The first lot used the Salin device approximately 8-10 hours/day. The control lot used the Salin for the same period of time but the device worked without the salt plates, so without forced ionization of the indoor air by salt sublimation.

In the lot I was noted a significant improvement of the clinical state and a subjective estimation “for better” have been seen by the patients, respectively by their parents especially in those that have been more seriously affected.

Objective symptoms of the disease, as sputum analysis, respiratory function, crackles at auscultation and FEV1, showed improvements from pre-treatment. In the control lot there were no changes similar to those from lot I.

On clinical examination, the patients receiving the active treatment were noted to have an increase of the sputum elimination at first stage followed by a significant reducing of its quantity, improvement of the respiratory functional syndrome, less crackles at auscultation and an improvement of FEV1. No patients receiving the active treatment have showed acute episodes of respiratory disease that should require another hospitalization for the duration of the treatment.

The authors concluded that forced ionization of the indoor air represents a natural and efficient treatment for respiratory diseases in patients with cystic fibrosis. This treatment could be used alongside with the classical therapy, doesn’t have any side effects and has a quite modest cost.

For more information, clinical studies and testimonials please click on salt therapy.

NB: The author grants reprint permission to opt-in publications and websites so long as the copyright and by-line are included intact and the article is not used in spam.

By: Livia Tiba

You can find the full original article at http://whatiscysticfibrosis.org/cystic-fibrosis/forced-indoor-air-ionization-by-salt-sublimation-may-improve-respiratory-symptoms-in-cystic-fibrosis

The Cells of CF

I thought this article did a good job explaining what is going on in the cells of a CFer, cause remember, it's not a lung disease. Cystic Fibrosis is a CELL disease.

Inhibition of Proteostasis Restores Ion Channels in CF Cells

Tuesday January 5, 2010

Our cells are full of enzymes that mediate activities like growth, metabolism, replication,transcription and cell signalling. They are all unique in their structure, and have evolved over time to perform the specific functions for which they are made. Some enzymes are hydrophillic(water-loving, or water soluble) and remain in the cytoplasm of the cell, while others arehydrophobic, thus more lipophillic. The lipophillic enzymes are generally found embedded in cell membranes and tend to have roles such as mediating the transport of small molecules and ions across the membrane. Cystic fibrosis transmembrane conductance regulator (CFTR) is one such membrane protein.

In order to study its structure and function, it is necessary to first purify a protein. Like all hydrophobic transmembrane proteins, study of CFTR is hindered because it is difficult to purify and study in a stable form. However, it has been determined that mutations in the gene encoding CFTR result in an improper protein structure, that folds incorrectly, is recognized as defective by cellular machinery, and is destroyed.

Without CFTR, chloride ion transport in the lungs is hindered, resulting in a mucus buildup characteristic of the disease. Efforts to treat CF by altering the gene or protein structures in patients have not been terribly effective, but last month a study was published that showedrestoration of ion transport could be achieved by controlling the actions of a class of enzymes responsible for proteostasis (destruction of proteins) called histone deacetylases (HDACs). A compound called suberoylanilide hydroxamic acid (SAHA), already approved by the FDA for treatment of lymphoma, was able to restore up to 28% of channel activity in isolated cell cultures from CF patients. The authors, Hutt et al., postulated that by preventing destruction of imperfect proteins, those polymorphisms that are not completely disfunctional can restore some ion exchange capacity in cell membranes.

Full article at http://biotech.about.com/b/2010/01/05/inhibition-of-proteostasis-restores-ion-channels-in-cf-cells.htm

Make sense??