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Runner Won’t Let Cystic Fibrosis Stop Him From Winning a 5K—or Qualifying for Boston

Original article on Runners World

“You just have to focus on what’s in front of you today, and breathe the best you can.”

When he was a kid, Michael Waltrip remembers getting bored at his brother’s soccer game, and asking his dad if he could kill some time running around the track. 

Waltrip was diagnosed with cystic fibrosis (CF) a few days after birth, so his father probably figured he’d last half a lap before breathing issues kicked in. 

But he took so many laps that they both stopped counting. Since then, he’s never really stopped. Not even when the breathing issues really did begin a few years ago.

A progressive, genetic disease, CF tends to worsen with age, and mainly affects the lungs and digestive system. The condition hampers the cells producing mucus, sweat, and digestive enzymes, often clogging airways and causing frequent lung infections, inability to gain weight, and difficulty absorbing nutrients.

For Waltrip, the digestive challenges have been lifelong, but he managed to avoid breathing problems until three years ago, when he turned 21. His doctors told him this may not have been simple luck—his running may have played a part in keeping him healthy, he said to Runner’s World.

When you run, the vibration that results from basically micro-jumping over and over is beneficial for the lungs, Waltrip said, because it helps to break up mucus. (Something most runners tend to experience, necessitating the perfect “snot rocket” form.) 

Since that first day of laps around the track, running had been a constant for Waltrip: After playing soccer himself as a kid, he switched to cross country in high school and logged 40 miles a week, then continued by joining the track team in college. 

Running may have helped ward off the breathing issues for some time, but when they did start several years ago, it was frightening. Waltrip recalled an awful feeling of being unable to take a full, deep breath. And that freaked him out.

“Until then, I think I didn’t acknowledge that I had CF because it wasn’t affecting me as much,” he said. “But then I came to the point where I couldn’t fall asleep because I couldn’t breathe properly, and I’d have to sit up and calm myself down for 30 minutes with breathing exercises.”

His running, which usually averaged around 60 miles a week, became much more of a struggle. Some runs would be okay, he said, but most would be filled with constant coughing and shallow breaths just to get the miles in.

“I still kept training, though,” Waltrip said. “I was being stubborn. That went on for six miserable months, before I finally decided that this was a big life lesson in accepting what was happening and getting help.”

His doctor put him on a daily treatment that included a nebulizer geared toward breaking up mucus, as well as a saline solution designed to irritate the lungs. Basically, he explained, your lungs don’t like salt, so they excrete water to balance it, and that helps break up the mucus and push it out. Waltrip also needed to inhale antibiotics, since people with CF who get bacterial infections in the lungs find those super hard to kick.

At the same time, he’s worked to stabilize his weight—an issue that’s always been a challenge. He can’t break down protein and fat very well because of his condition, and adding 60 to 80 miles of running a week on top of that means near-constant eating to keep from being too underweight. 

Despite these obstacles, though, he’s back in run-all-the-laps form. 

Waltrip recently won the Fairfax, Virginia-based Run Your Heart Out 5K in 16:02, and last July, he qualified for Boston during his first marathon attempt in San Francisco. Ditching his stubbornness and embracing daily treatment has helped him stay regimented, he said, and he’ll be at the Boston starting line in April.

“Just to be able to run with CF is kind of crazy and awesome,” he said. “But, like anything, you just have to focus on what’s in front of you today, and breathe the best you can.”

Immunotherapy May Be Promising Strategy to Treat Chronic Infections of P. aeruginosa in CF Patients

Original article on CF News Today

Blocking the interaction between two molecules involved in immune restraining mechanisms — called PD-1 and PD-L1 — may be an effective therapeutic strategy to boost the immune system and treat chronic infections of Pseudomonas aeruginosa in cystic fibrosis (CF) patients, according to a recent study.

The study, “Pseudomonas aeruginosa colonization causes PD-L1 overexpression on monocytes, impairing the adaptive immune response in patients with cystic fibrosis,” was published in the Journal of Cystic Fibrosis.

Chronic lung infections by P. aeruginosa —a highly antibiotic-resistant bacteria — are the leading cause of death among CF patients.

The high frequency of infections in CF patients suggest they have an impaired immune system. Furthermore, previous studies have shown that these patients have what is called an endotoxin tolerance, meaning a reduced responsiveness to pathogens following a first contact, leading to a desensitization of immune cells against them.

Researchers have proposed that the passage of bacteria to the bloodstream, inducing a systemic exposure to their LPS — a major component of the cell wall of some bacteria, including P. aeruginosa, that is recognized by the body’s immune system as foreign —, either attached to the membrane or in a soluble form, may explain the endotoxin tolerance observed in CF patients.

Recent evidence has shown that PD-L1 is a marker of endotoxin tolerance. PD-L1/PD-1 interaction has emerged as an important mechanism in the immune response, where the binding of PD-L1, present in many cells, to its PD-1 receptor on immune T-cells prevents the activation of T-cells — a type of white blood cell that fights infections and cancer cells.

Targeting and blocking this interaction has been shown to promote T-cell activation, and to be associated with a protective effect against infections.

However, the potential role of PD-L1/PD-1 interaction in CF, and especially in CF patients infected by P. aeruginosa, remains unexplored.

Researchers in Madrid evaluated the levels of PD-L1 and PD-1 in CF patients, and the potential association between PD-L1/PD-1 interaction and P. aeruginosainfection.

The team analyzed the levels of PD-L1 in monocytes — a type of white blood cell that is in the frontline of infection, and communicates with T-cells — and of PD-1 in T-cells of 32 CF patients, 19 of them infected by P. aeruginosa, and of healthy volunteers. These cells also were grown in the lab to assess their proliferation and immune responses.

Results showed that CF patients had significantly higher levels of PD-L1 in monocytes and PD-1 in T-cells than healthy people, and that PD-L1 levels — both in monocytes and in a soluble form in the blood — were even higher in CF patients infected with P. aeruginosa.

These data, combined with the fact that CF patients infected with P. aeruginosaalso showed a significant impairment in T-cell proliferation, highlighted an association between P. aeruginosa infection and an increased suppression of T-cells.

In accordance, additional analysis showed that endotoxin tolerance in monocytes was stronger in CF patients infected with P. aeruginosa than in those who were not.

Interestingly, the addition of an antibody that blocks PD-L1/PD-1 interaction to T-cells from patients infected with the bacteria significantly increased the proliferation of T-cells to levels almost comparable to those of healthy people and patients without the infection, suggesting this type of approach could revert the impaired immune response and benefit these CF patients.

The team also found evidence strengthening the hypothesis that bacteria/LPS presence in the blood induces increased levels of PD-L1 and endotoxin tolerance, as the levels of PD-L1 in monocytes from healthy people were significantly increased when in contact with isolated LPS of P. aeruginosa, or with blood of CF patients infected with the bacteria.

This PD-L1 increase with blood of infected CF patients was reduced when monocytes were pretreated with colistin (polymyxin E), a potent antibiotic that neutralizes or absorbs LPS. CF patients treated with colistin had lower levels of soluble PD-L1 in their blood.

These results suggest that colistin could be used to reduce the effects of bacteria passage to the bloodstream in CF patients infected with P. aeruginosa. Nonetheless, the team noted that future clinical trials are needed to confirm this hypothesis.

Overall, based on the results, the team concluded that “Pseudomonas aeruginosa colonization in patients with CF was associated with PD-L1 overexpression and impaired T-cell response, and LPS from this pathogen induced the observed phenotype.”

“Altogether, our results suggest the possibility of studying antibiotics and antiPD-1/PD-L1 antibody combination as a new potential treatment to provide clinical benefits to patients with P. aeruginosa colonization,” the researchers added.

Patients with lung disease could find relief by breathing in messenger RNA molecules

Original article on Science Daily.

Messenger RNA, which can induce cells to produce therapeutic proteins, holds great promise for treating a variety of diseases. The biggest obstacle to this approach so far has been finding safe and efficient ways to deliver mRNA molecules to the target cells.

In an advance that could lead to new treatments for lung disease, MIT researchers have now designed an inhalable form of mRNA. This aerosol could be administered directly to the lungs to help treat diseases such as cystic fibrosis, the researchers say.

“We think the ability to deliver mRNA via inhalation could allow us to treat a range of different disease of the lung,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study.

The researchers showed that they could induce lung cells in mice to produce a target protein — in this case, a bioluminescent protein. If the same success rate can be achieved with therapeutic proteins, that could be high enough to treat many lung diseases, the researchers say.

Asha Patel, a former MIT postdoc who is now an assistant professor at Imperial College London, is the lead author of the paper, which appears in the Jan. 4 issue of the journal Advanced Materials. Other authors of the paper include James Kaczmarek and Kevin Kauffman, both recent MIT PhD recipients; Suman Bose, a research scientist at the Koch Institute; Faryal Mir, a former MIT technical assistant; Michael Heartlein, the chief technical officer at Translate Bio; Frank DeRosa, senior vice president of research and development at Translate Bio; and Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute.

Treatment by inhalation

Messenger RNA encodes genetic instructions that stimulate cells to produce specific proteins. Many researchers have been working on developing mRNA to treat genetic disorders or cancer, by essentially turning the patients’ own cells into drug factories.

Because mRNA can be easily broken down in the body, it needs to transported within some kind of protective carrier. Anderson’s lab has previously designed materials that can deliver mRNA and another type of RNA therapy called RNA interference (RNAi) to the liver and other organs, and some of these are being further developed for possible testing in patients.

In this study, the researchers wanted to create an inhalable form of mRNA, which would allow the molecules to be delivered directly to the lungs. Many existing drugs for asthma and other lung diseases are specially formulated so they can be inhaled via either an inhaler, which sprays powdered particles of medication, or a nebulizer, which releases an aerosol containing the medication.

The MIT team set out to develop a material that could stabilize RNA during the process of aerosol delivery. Some previous studies have explored a material called polyethylenimine (PEI) for delivering inhalable DNA to the lungs. However, PEI doesn’t break down easily, so with the repeated dosing that would likely be required for mRNA therapies, the polymer could accumulate and cause side effects.

To avoid those potential side effects, the researchers turned to a type of positively charged polymers called hyperbranched poly (beta amino esters), which, unlike PEI, are biodegradable.

The particles the team created consist of spheres, approximately 150 nanometers in diameter, with a tangled mixture of the polymer and mRNA molecules that encode luciferase, a bioluminescent protein. The researchers suspended these particles in droplets and delivered them to mice as an inhalable mist, using a nebulizer.

“Breathing is used as a simple but effective delivery route to the lungs. Once the aerosol droplets are inhaled, the nanoparticles contained within each droplet enter the cells and instruct it to make a particular protein from mRNA,” Patel says.

The researchers found that 24 hours after the mice inhaled the mRNA, lung cells were producing the bioluminescent protein. The amount of protein gradually fell over time as the mRNA was cleared. The researchers were able to maintain steady levels of the protein by giving the mice repeated doses, which may be necessary if adapted to treat chronic lung disease.

Broad distribution

Further analysis of the lungs revealed that mRNA was evenly distributed throughout the five lobes of the lungs and was taken up mainly by epithelial lung cells, which line the lung surfaces. These cells are implicated in cystic fibrosis, as well as other lung diseases such as respiratory distress syndrome, which is caused by a deficiency in surfactant protein. In her new lab at Imperial College London, Patel plans to further investigate mRNA-based therapeutics.

In this study, the researchers also demonstrated that the nanoparticles could be freeze-dried into a powder, suggesting that it may be possible to deliver them via an inhaler instead of nebulizer, which could make the medication more convenient for patients.

TranslateBio, a company developing mRNA therapeutics, partially funded this study and has also begun testing an inhalable form of mRNA in a Phase 1/2 clinical trial in patients with cystic fibrosis. Other sources of funding for this study include the United Kingdom Engineering and Physical Sciences Research Council and the Koch Institute Support (core) Grant from the National Cancer Institute.

Losing disability insurance is a possible nightmare for those with CF

Original article on CBS This Morning

Megan Willis lives with cystic fibrosis, a deadly disease that causes extensive lung damage. The 22-year-old said she spends around six hours a day administering medications and therapy, and that the disease frequently causes infections and other complications.

With the condition, Willis qualified as a disabled adult for Social Security benefits on living expenses. About 10 million other Americans too disabled for work also get the stipend, called Disability Insurance. More importantly, having Social Security gave Willis access to Medicaid, which paid her annual health care costs of over $100,000.

But in March, Social Security sent her a letter saying her health had improved since the last review of her case and that she was able to work. This was news to Willis.

“My health has only gotten worse in the past year,” Willis told CBS News chief medical correspondent Dr. Jon LaPook.

Despite that, her Social Security benefits were terminated and she lost Medicaid. Since she lives in Florida, one of 14 states without expanded Medicaid, she had no other way to get it. Her family can’t afford private insurance.

While the medical bills mounted, she began law school.

“I don’t want to just stay stagnant and you know, depressed, looking at the four walls of my room,” Willis said. “I want to move up in the world even if you know it’s going to be hard.”

Willis also contacted attorney Beth Sufian, who runs the Cystic Fibrosis Legal Hotline and has cystic fibrosis herself. Sufian said, “We’ve seen a five-times increase in the number of people with cystic fibrosis that have been reviewed in the past 18 months. And we think that Social Security is targeting young people with chronic illness in an effort to reduce the number of people getting benefits.”

By law, disability claims are periodically reviewed to see if recipients are still eligible for benefits. Over the last decade, to combat a backlog, full medical reviews quadrupled to an expected 900,000 this year.      

“It really is a life or death situation for all of our clients when they lose their benefits,” Sufian said.   

In Willis’ case, Social Security ultimately reconsidered and she was able to get back on disability in November. She was hospitalized around Thanksgiving, and Medicaid kicked in and the bills were covered, her mother Wendy said.

But Willis’s lawyer still has about 200 pending cases of people with cystic fibrosis who are first getting reviewed and those who are appealing.

***

Losing disability insurance can have devastating consequences for those with CF. Our very own Vice President, Beth Sufian, helps many individuals get on and stay on disability. For the full story go to https://www.cbsnews.com/…/what-happens-when-someone-loses-…/

Insufficient antibiotics available for cystic fibrosis patients: Study

Turns out, the majority of patients with cystic fibrosis may not achieve blood concentrations of antibiotics sufficiently high enough to effectively fight bacteria responsible for pulmonary exacerbations, thus leading to worsening pulmonary function.

Cystic fibrosis, a genetic condition that affects about 70,000 people worldwide, is characterised by a buildup of thick, sticky mucus in patients’ lungs. There, the mucus traps bacteria, causing patients to develop frequent lung infections that progressively damage these vital organs and impair patients’ ability to breathe.

A recent study led by researchers at Children’s National Health System shows that it’s impossible to predict solely from dosing regimens which patients will achieve therapeutically meaningful antibiotic concentrations in their blood. The findings were published online in the Journal of Pediatric Pharmacology and Therapeutics.

These infections, which cause a host of symptoms collectively known as pulmonary exacerbations, are typically treated with a combination of at least two antibiotics with unique mechanisms. One of these drugs is typically a Beta-lactam antibiotic, a member of a family of antibiotics that includes penicillin derivatives, cephalosporins, monobactams and carbapenems.

Although all antibiotics have a minimum concentration threshold necessary to treat infections, Beta-lactam antibiotics are time-dependent in their bactericidal activity. Their concentrations must exceed a minimum inhibitory concentration for a certain period. However, study’s lead author Andrea Hahn explained that blood concentrations of Beta-lactam antibiotics aren’t typically tracked while patients receive them.

Since antibiotic dosing often doesn’t correlate with cystic fibrosis patients’ clinical outcomes, Dr. Hahn and other researchers examined whether patients actually achieved serum antibiotic concentrations that are therapeutically effective.

In addition, all the patients underwent pulmonary function tests at the start of their exacerbations and about once weekly until their antibiotic therapy ended.

Using the data points, the researchers constructed a model to determine which patients had achieved therapeutic concentrations for the bacteria found in their respiratory secretions. They then correlated these findings with the results of patients’ pulmonary function tests. Just 47 per cent of patients had achieved therapeutic concentrations. Those who achieved significantly high antibiotic exposure had more improvement on their pulmonary function tests compared with patients who didn’t.

Paradoxically, they discovered that although each patient received recommended antibiotic doses, some patients had adequately high serum antibiotic concentrations while others did not.

Another way to ensure patients receive therapeutically meaningful levels of antibiotics is to develop new models that incorporate variables such as age, gender, and creatinine clearance–a measure of kidney function that can be a valuable predictor of metabolism–to predict drug pharmacokinetics.

Using findings from this research, Dr. Hahn adds, Children’s National already has implemented an algorithm using different variables to determine antibiotic dosing for patients treated at the hospital.

Original article here.

An artist who sees on his own terms

By CATHERINE SHAFFER

Detroit artist Brendan Patrick lost his vision, and nearly his life, to cystic fibrosis. Now he’s making the most of the time he’s been given by creating art and raising awareness of his disease.

At first glance, Brendan Patrick’s studio looks like any artist’s studio. It’s full of paints, supplies, and canvases filled with bright colors. But look a little closer, and you’ll see everything is labeled in braille. Brendan is banging a jar of red paint against his desk to get the lid open. He’s wearing paint splattered overalls and dark sunglasses.

He’s showing us his technique: “I dip my paintbrush in some paint. And I just kind of follow the line with my left hand while the brush is in my right hand. And, the key is, hopefully I stay in the lines. We’ll see if that happens. Well, you guys will see if that happens,” Brendan says, laughing.

Brendan lost his vision a decade ago. Before that, he was a tattoo artist. And in his free time he learned to play the guitar and started a band. All while living with a serious illness: cystic fibrosis.

Cystic fibrosis causes progressive damage to the lungs. Brendan was in the hospital repeatedly. By the time he was twenty-six, it seemed like his time was up. In 2008, he spent five months in intensive care waiting for a lung transplant.

“While I was on my ventilator, all I was doing was painting. Twenty-four seven, I probably painted maybe a hundred paintings. I was in the ICU, in my own private room, and it looked like an art gallery,” Brendan says.

Brendan’s lung transplant was a success. But he had a rare complication. He lost his vision.

Rob Cousineau is a longtime friend of Brendan’s, and he’s filming a documentary about him. He remembers the aftermath of Brendan’s devastating loss.

Cousineau says, “Brendan has all of this time now gifted to him with this new lung transplant and he can’t see, so he has nothing to do with the time he has left.”

Brendan’s friends and family stood by helplessly as he spiraled into depression. This went on for about two years. Then a friend suggested he use puffy paint to outline his designs. And that got him painting again.

Something really interesting happened to Brendan’s art after he was blind: a new style emerged on the canvas.

“I can create rooms in my brain. I can create images, and I can kind of paint a person’s face that I’ve never seen…If I’m dipping my paintbrush into yellow, I can see the yellow come onto the canvas. I guess seeing in my own terms now,” says Brendan.

Ten years later, Brendan’s style is basically the same as it was before he was blind. It’s full of bright colors and characters from horror and science fiction. But there’s something different about it now. Like you’re seeing directly into Brendan’s mind. And people love it.

“Some of the stuff he does, it’s ridiculous how good it is for the fact that he’s blind, you can see that he’s blind. The stuff all just works.”

That’s another artist, Evans Tasiopoulos, at a fundraiser for cystic fibrosis featuring Brendan’s art. Dozens of artists are painting blindfolded in Detroit’s Tangent gallery, trying to copy Brendan’s process. They’re doing this for the first time, and it’s mostly going hilariously wrong for them.

Tucked away in a corner, Brendan sits on the floor with his paints and canvases. He says he’s painting a fluffy bunny rabbit. It’s grotesque — and cute. He makes it look easy.

Brendan’s not exactly grateful he lost his vision. But he is having a lot of success because of it.

“It moves some paintings, so that’s positive, right. But, with that being said, my story isn’t really about me dwelling on my misfortunes. It’s about what I’ve done after,” says Brendan.

And what he’s done after is create a tremendous amount of art, and music. Most people think they have plenty of time to accomplish their goals in life. Brendan’s gift is that he has never taken his time for granted.

Original article here.

Juggling Responsibilities and Compliance – Guest blog by LMK Scholarship Winner

By: Mike Miccioli

I went to high school in Nashville, Tennessee and am currently a freshman at Harvard. Growing up in Nashville, I always focused on academics and staying healthy. On the academic side, I have always had an interest in mathematics, and physics is a fascinating way to apply math to science and the universe. I took all the toughest courses in math and science, and I competed in every math competition and Science Olympiad contest available. I did applied mathematics research at Vanderbilt University the summer after my junior year of high school, and different research during my senior year in condensed matter physics. On top of this hefty workload, my school required all its students to play sports after school year-round. With all of these obligations and many hours of homework each night after sports, working in my CF therapies was not easy; however, from an early age I learned the lesson that I had to prioritize my CF therapies that were necessary to keep me healthy and enable me to pursue my academics and sports. I had to be disciplined, and I got up early each day before school to make sure I did all my vests and nebulizers in the morning. There was a second round each evening, and I would always try to combine homework with both the morning and evening sessions. If a special circumstance would throw my schedule off and interfere with my therapies, I always made them up at different times during the same day; it was a given that I couldn’t miss therapies.

Compliance with the therapies that are available to us nowadays is crucial to having a good outcome with CF. There is generally a vast difference between the outcomes of patients who do their best to comply with their therapies every day and those who have a hard time completing theirs on a regular basis. I have always stayed aware of this fact and used it to motivate me to be compliant, and I believe it has paid off.

This fall I made the transition to my first semester in college, 1200 miles away from home and my support network. The first adjustment was being responsible for remembering to do everything without prompting from my parents. That wasn’t too difficult, and a bigger challenge was learning how to be more flexible in how I achieved my full compliance despite the fact that my schedule was different every day. Reflecting back on my years prior to college, my schedule was the same nearly every day, and this helped me stay disciplined in keeping up with my therapies. In college, I have had to look at each day and determine when I am going to fit in my routine as I meet all my academic obligations. Having completed my first semester, while it was frustrating at first, I eventually fell into a rhythm — from having nighttime labs one day to having an overloaded afternoon the next, eventually I encountered all the different scenarios I would be faced with, and it became easier to deal with each day’s changes.

I am continuing my studies of math and physics at Harvard and am currently in the process of applying for research opportunities for this summer. At this point, I am thinking that I want to pursue a career in scientific research. I guess one of the main reasons I feel this way is because I have personally benefited from modern advancements in medicine. I currently take one of the CFTR modulator drugs and have had good results with it, and it reminds me every day of how people can benefit from cutting edge research and have their lives changed in meaningful ways. I hope to be able to contribute back to the scientific community and perhaps some day make a difference for others.

This also relates back to the point I was making before about working hard to be as compliant as possible with your CF therapies. CF research has made amazing strides, and it appears that significantly improved CFTR modulators will be available to as many as 90% of those of us with CF sometime in 2019. The healthier we are when these new therapies become available, the better positioned we will be to take advantage of their benefits to the maximum degree possible. That is the other big reason to try and stay compliant. So, in conclusion, I want to encourage everyone to remember that while it is difficult to make compliance a priority day after day, without a break, particularly when you are in college with new vistas to explore and great demands for your time, it is worth it, and you will reap the benefits in the short run and even more so down the road when new therapies become available.

Aridis Enrolling CF Patients to Test AR-501 in Chronic Lung Infections

By:
ALICE MELÃO

Aridis Pharmaceuticals has enrolled the first healthy participant in its Phase 1/2a clinical trial to evaluate the antibacterial potential of its investigational candidate, AR-501 (gallium citrate), against chronic lung infections in patients with cystic fibrosis (CF).

The study (NCT03669614) is expected to enroll approximately 48 healthy adult volunteers and 48 adult CF patients with chronic lung infections across 15 sites in the United States.

Participants will be randomized to receive one of three doses of AR-501, or a placebo, self-administered once a week using a hand-held nebulizer.

The company expects to announce results from Phase 1 during the fourth quarter of 2019, and from Phase 2a in the fourth quarter of 2020.

“We are pleased to initiate this exciting program with the first subject enrolled,” Wolfgang Dummer, MD, PhD, chief medical officer of Aridis, said in a press release. “Through this trial, we anticipate safety, pharmacokinetic, and exploratory efficacy data that will enable us to further explore the potential of AR-501 in the treatment of life-threatening bacterial infections in cystic fibrosis patients.”

AR-501 is an inhalable formulation of gallium being developed to treat pulmonary bacterial infections. It works by starving bacteria of iron, and inhibiting their iron-dependent metabolic processes necessary for the infection to progress, a mechanism very different from that of common antibiotics.

Preclinical studies have demonstrated that AR-501 holds a broad antibacterial activity with unique benefits, compared to current standard-of-care antibiotics, working against antibiotic-resistant strains such as Pseudomonas aeruginosa and B. cepaciaaccording to the company.

Also, data from a Phase 2 clinical trial (NCT02354859) showed that intravenous gallium is safe and can effectively improve the lung function of CF patients.

“The recent safety and efficacy demonstration of intravenous gallium from a Phase 2 clinical study in CF patients gives us optimism of the prospect inhaled delivery of gallium (AR-501), which is a more direct, local route of delivery to the site of infection in the lungs and less systemic exposure,” Dummer said.

The new Phase 1/2a trial is being conducted in collaboration with the Cystic Fibrosis Foundation (CFF), and is led by Noah Lechtzin, MD, director of the Adult Cystic Fibrosis Program and associate professor of medicine at Johns Hopkins University.

The U.S. Food and Drug Administration recently granted Fast Track Designation and Qualified Infectious Disease Product Designation (QIDP) to AR-501. These are expected to support and expedite the therapy’s development and regulatory review.

Original article: https://cysticfibrosisnewstoday.com/2018/12/14/aridis-started-enrolling-in-phase-1-2a-trial-to-test-ar-501-antibacterial-potential/

For Use in CF, New 2-in-1 Powder More Effective Against Resistant Bacteria

https://cysticfibrosisnewstoday.com/2018/12/18/new-powder-inhalation-more-effective-killing-antibiotic-resistant-bacteria/?utm_source=Cystic+Fibrosis&utm_campaign=c31e0676bf-RSS_MONDAY_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b075749015-c31e0676bf-71418393

By Albert Molano

Originally published in Cystic Fibrosis News Today

12/18/2018

Purdue University researchers have invented a new way of delivering two antibiotics (colistin and ciprofloxacin) deep into the lungs of cystic fibrosis (CF) patients, enabling much more effective killing of antibiotic-resistant bacteria without exposing patients to high systemic doses of these therapies.

“We are providing a promising option to fight the global crisis of antimicrobial resistance,” Qi (Tony) Zhou, PhD, assistant professor at Purdue’s College of Pharmacy, who led the research team, said in a press release.

Respiratory infections caused by multidrug-resistant bacteria in CF patients can be deadly because they are resistant to most available antibiotics. In addition, therapies given intravenously (by injection into the vein) or orally have a hard time reaching the lungs, potentially requiring high doses for the therapy to be effective.

Last-resort antibiotics can still be effective, but these can be very toxic if they are given systemically. Colistin, for example, can damage the kidneys.

The existing alternative is to nebulize the antibiotics and deliver them directly into the lungs, which increases their local concentrations while reducing the risk of systemic toxicity. However, this requires expensive and complicated delivery devices, and prolonged administration times.

Now, Zhou’s team has succeeded in combining two antibiotics — colistin and ciprofloxacin — into a single particle that can be delivered as a dry powder.

According to the team, with this new formulation, more than 60 percent of the antibiotics reach the lungs, as opposed to only 10 percent with a jet nebulizer. In addition, the dry formulation offers improved chemical stability, and it is easier to use than conventional inhalation products.

“It has been a worldwide challenge to incorporate two antibiotics with different chemical properties into a single particle. Our novel formulation allows for a much more effective killing of drug-resistant bacteria in the deep lungs as two synergistic antibiotics can be simultaneously delivered to the same infection site,” Zhou said.

The team believes this technology can be applied to several antibiotic and compound combinations, potentially saving tens of thousands of lives from several deadly lung infections, including those affecting CF patients and people with ventilator-assisted pneumonia.

The Purdue Office of Technology Commercialization has filed a patent for the new technology, and researchers are looking for partners to continue its development.

Congratulations to Our Scholarship Winners!

The US Adult CF Association (USACFA) is excited to announce our recipients of the Lauren Melissa Kelly Scholarship for the Spring of 2019.

In our evaluation, we look for students who demonstrate tremendous academic achievement, community involvement and a powerful understanding of how having CF matched with these achievements places them in a unique situation to gain leadership roles within the community. Our scholarship is open to all pursuing any degree, from associates to Ph.Ds. We believe that any higher education is a strong foundation for advocacy and involvement in CF.

We are pleased to announce Rebecca Cedillo and Michael Miccioli as the recipients of this semesters’ scholarship. Congratulations to them! They will be awarded $2500 each.

Both of our recipients demonstrated the leadership, intelligence, and drive of Lauren Melissa Kelly. We at USACFA look forward to seeing them further develop their leadership and advocacy in the cystic fibrosis community.

We are excited to announce more scholarship opportunities coming soon! Please stay tuned for more information. For questions, please contact us at scholarships@usacfa.org.