In CF, Low-dose Antibiotics Aid Bacterial Diversity in Airways, But at a Cost

As published on CF News Today, BY JOSE MARQUES LOPES, PHD

Using lower, or suboptimal, doses of antibiotics to treat lung infections in children and young adults with cystic fibrosis (CF) leads to fewer changes in airway bacterial diversity compared to therapeutic (higher) antibiotic exposure.

The findings also suggested, however, that patients receiving therapeutic doses had greater improvements in lung function.

The research, “Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis,” was published in the journal Scientific Reports.

People with CF often have recurrent lung infections that gradually worsen their lung function. Treatment of these infections, known as acute pulmonary exacerbations (APEs), is typically based on antibiotics directed at pathogens such as Pseudomonas aeruginosa. However, repeated dosing with antibiotics has been suggested as the cause of decreased microbial diversity in the airways, which, in turn, could worsen lung function.

Despite current guidelines recommending higher antibiotic dosing regimens in people with CF, data from the U.S. indicate that beta-lactams — which include penicillin — were given in doses below the guidelines 38–53% of the time.

Although CF patients often do not achieve therapeutic doses of antibiotics to clear infections, which means that their blood levels of antibiotics do not increase sufficiently for effective treatment, it remains to be determined whether short courses of subtherapeutic doses alter microbial diversity, compared to therapeutic doses.

Aiming to address this question, researchers recruited 20 patients, ages 1-21, who were treated for APEs with intravenous infusion of beta-lactam antibiotics at Washington, D.C.’s Children’s National Health System.

Four samples of respiratory fluid were collected from each patient — when they were experiencing an APE, when they were doing well, right after antibiotic treatment, and at least 30 days later. Genetic testing determined the type and relative abundance of bacteria in each sample.

Blood samples and data on lung function were also collected during antibiotic treatment. Plasma antibiotic levels and bacterial minimum inhibitory concentrations (MICs) were used to determine therapeutic versus subtherapeutic antibiotic exposure.

Of note, to achieve effective bacterial killing, the serum concentration of an antibiotic must be above the MIC of the bacteria for a certain amount of time. Subtherapeutic exposure was thereby defined as insufficient time above MIC.

A total of 31 APEs were reported over the study period, from March 2015 to August 2016, and only approximately 14 (45%) of the antibiotic courses given were considered therapeutic. Most treatment regimens (25 out of 31 antibiotic regimens administered) included a single beta-lactam antibiotic.

Patients in the therapeutic group (11 patients, median age 9) had better lung function, and were less likely to receive inhaled antibiotics at study start, compared with the nine patients (median age 14) receiving subtherapeutic doses — 45% versus 100%, respectively.

At exacerbation onset, people in the therapeutic group showed a greater trend toward having a normal flora, compared to the subtherapeutic group (43% versus 12%), as well as increased abundance of Gemella, and a decrease in unclassified Enterobacteriaceae.

There was no significant difference in the presence of Pseudomonas aeruginosa or Staphylococcus aureus between the therapeutic and subtherapeutic groups.

As for antibiotic use, participants in the therapeutic group received ceftazidime (a more narrow spectrum beta-lactam) more often (86% versus 41%), and less frequently meropenem (a broad spectrum beta-lactam; 21% versus 59%) than those in the subtherapeutic group.

Those in the therapeutic group also had a significantly shorter time from end of treatment to post-recovery — 51 versus 79 days.

At both end of treatment and post-recovery, patients in the therapeutic group had decreased bacterial diversity in their airways, which contrasted with those receiving subtherapeutic doses — who showed minimal changes or higher diversity more than one month after treatment.

Unlike participants in the therapeutic group, who showed increased or decreased relative abundance of specific bacterial genera compared to baseline, those in the subtherapeutic group showed no changes.

“With the subtherapeutic treatment group, this could represent a ‘basement effect’ where it is harder to decrease diversity when it is already low to start,” Andrea Hahn, MD, the study’s lead author, said in a press release.

Also, “patients in the subtherapeutic group had more advanced disease than those in the therapeutic group, which may influence the findings,” Hahn said.

Data further showed that receiving therapeutic antibiotics was associated with a trend toward greater improvement in lung function.

“Thus, the conclusion should not be drawn that because subtherapeutic antibiotics have less impact on changes in microbial diversity, it could be used as a strategy to prevent declining lung function,” the scientists said. “This is likely a reflection of disease severity, antibiotic exposure, and antibiotic resistance.”

The researchers believe that repeated subtherapeutic courses of antibiotics could lower microbial diversity without clearing infections, causing progressive lung dysfunction. Closer monitoring of antibiotic levels in blood to ensure that each exacerbation is treated with therapeutic-level dosing could be an effective answer, Hahn said.

“What this study shows is that levels of the antibiotics we give probably play a role in patients’ ability to recover baseline diversity,” Hahn said. “If we pay more attention to drug levels when using these types of antibiotics to ensure that dosing is sufficient, we could potentially improve patients’ clinical outcomes over time.”

Window of opportunity for treatment of early cystic fibrosis lung infections

Technical University of Denmark

CF-patients have a genetic defect which results in dehydrated sticky mucous in the lungs, leading to severe and persistent lung infections often caused by Pseudomonas aeruginosa.

The research shows that within the first two to three years after infection with P. aeruginosa, the bacteria are already adapting rapidly to the environment, growing slower and optimizing their fitness to survive.

“Across all of our patients within the first three years, the bacteria on average slow their growth rates significantly and they reduce their susceptibility to ciprofloxacin, a first line drug in treatment of CF-patients. This means that one should pay extra close attention in this period of time to avoid the infection becoming persistent,” says Jennifer Bartell, Postdoc at The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain) and co-first author.

Looking beyond antibiotic resistance

Clinicians usually focus on detecting antibiotic resistance during infections, and this appears to be an effective way to follow the development of short-term acute infections.

Antibiotic resistant bacteria are identified by their ability to survive above a specific concentration of an antibiotic. The researchers saw a rapid increase in the concentration of antibiotics that the bacteria could tolerate. But at the same time, few bacteria achieved detectable antibiotic resistance in the early infection period of CF. The researchers suspect this pre-resistance adaptation to be an underused marker of progression in the infection. This pre-resistance adaptation likely occurs in other persistent infections, such as chronic obstructive pulmonary disease (COPD).

Besides looking for antibiotic resistance, clinicians also monitor bacterial mucoidity — a trait where bacteria produce a protective, slimy coating, as a marker of a chronic infection.

But according to the new study, bacteria can become persistent and resilient to treatment regardless of the appearance of mucoidity. Other bacterial traits such as the ability to attach to surfaces and aggregate in biofilms — hefty structured layers of adherent cells — evolve more consistently in these persisting infections than mucoidity and may serve as a better sign of early chronic infection.

“We can see which traits might actually be valuable for the clinicians to monitor in addition to antibiotic resistance,” says Lea Sommer, Postdoc at Rigshospitalet and co-first author.

Potential for new diagnostic tools

The researchers identified these important evolving traits of P. aeruginosa by screening 443 isolates from 39 young cystic fibrosis (CF) patients over a ten-year period and mapping traits adapting in tandem using statistical modeling approaches. Usually, studies focus on bacterial isolates collected from older CF-patients with chronic infections, who have become multi-drug resistant and already have adapted to the human lungs.

These results emphasize that trait evolution measurements are important and should not be neglected, even though genomic tests are advancing.

“In this early phase, the bacteria change a lot and become much more robust, but the doctors do not necessarily see this with current clinical measurements,” says Lea Sommer.

Going forward, the researchers wish to find out how the adapting bacteria respond to a larger panel of antibiotics that are used to treat patients. Armed with this comprehensive map of evolutionary pathways, clinicians would have a much better chance of categorizing the infection and, hence, take the necessary precautionary steps.

“In the clinic, doctors would potentially be able to take a single patient’s bacterial screening data and analyze how this patient responds to the current treatment. As we gain experience with more patients, it will be easier to assess what can be done to stop the transition to chronic infection, “says Jennifer Bartell.

Thus, this could pave the way for developing more fine-tuned personalized treatments for all patients suffering from continuous persisting infections, such as CF, COPD, and perhaps diabetics with chronically infected wounds.

Original article: https://www.sciencedaily.com/releases/2019/03/190304121505.htm

Nutrition – Patient Task Force Meeting

By: Melissa Shiffman

Growing up, I had an unhealthy relationship with food. My brother and I both were diagnosed with Cystic Fibrosis as children. He was pancreatic insufficient, painfully thin and took handfuls of enzymes. Meal times were filled with constant fighting as my parents tried to force him to eat. Meanwhile, I was pancreatic sufficient with a very healthy appetite. Our body shapes could not be more different! He was skin and bones and I was chubby. As I got older, “chubby” was socially unacceptable. I was twelve the first time I went on the “hotdog diet!”

I have no real memory of fresh fruit and vegetables being readily available. Instead, our refrigerator was filled with high calorie, high fat foods to encourage my brother to eat: Kit Kats, Nestle Crunch, ice cream, Sustacal puddings. I was told not to eat his food, so I snuck it and ate in my room. I gained more weight. My brother made fat faces to get under my skin as I sucked in my cheeks back to him.

Like a normal pre-teen, I became self conscious about my appearance.Everyone talked about fad diets and losing weight. I absorbed that being thin was ideal. By the end of 8th grade, I convinced myself that, if I read the ingredients in things like Oreos, I would find a way to be disgusted. Eventually, I talked myself out of eating most foods except for grapefruit and canned tuna without mayo. I ate minimally and cut out sweets. I lost a lot of weight, started to look more like my brother (but less sickly) and revelled in the compliments on my weight loss.  

I know this is not the normal CF story. However, it is so important to recognize our relationship with food and to rectify our lack of education on eating well when you are underweight or gaining weight on modulators. Therefore, I am looking forward to Dr.Tonja Gonska (gastroenterologist at Sick Kids Hospital in Toronto) discussing healthy eating vs. high fat/high caloric intake, body composition vs. BMI and how nutrition plays a role in healthy weight gain for women with CF at the CFReSHC Patient Task Force meeting on Thursday March 21, 2019 from 3-5 pm EST.

Attendees can share their personal experiences, help develop potential research questions to be addressed by the CFReSHC research advisory panel and receive an Amazon gift card for their time.  For more information on CFReSHC and for login information email CFReSHC at info@CFReSHC.org.  

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/

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.