Friday, October 9, 2015

NACFC 2015--Details from Day 1

This morning, the action began at 10 a.m. with a host of workshops.  Because there are always multiple interesting talks happening at the same time, Brock and I decided to divide and conquer to take in the most information.  Here are the most interesting nuggets from my morning.

I was anxious to hear the results of the European Gene Therapy Trials at the NACFC last year, but the UK team backed out last minute in order to complete their data collection process.  I was able to see their data earlier this year in a videotaped presentation by Dr. Alton, but this was the first time that the trial results have really been shared at a meeting like this, with the professional CF community at large. 

A Randomized, Double-blind, Placebo-controlled Trial of Repeated Nebulization of Non-viral CFTR Gene Therapy in Patients with Cystic Fibrosis.  Presented by Dr. Eric Alton

While research in the U.S. has been focused on the “small molecule” approach to treating CF, scientists in the UK have poured a tremendous amount of time and energy into gene therapy.  The UK CF Gene Consortium has been working for years on this project, and has encountered considerable obstacles along the way.  The most formidable challenge has been identification of an effective vector to transmit genes inside the lung cells of CF patients.  Many viral vectors were tested and abandoned due to the high inflammatory response they elicited (infection by virus is one way to breach the cell wall and gain access to the DNA held inside, but was found to cause too much collateral inflammatory damage to be an effective candidate).  Ultimately, a lipid (fat) vector was chosen to perform a phase 2b placebo controlled trial in humans.  Trial participants were asked to nebulize a gene therapy solution once a month (approximately 40 minutes to complete treatment). Ultimately, the study showed statistically significant improvements in FEV1.  

Patients exhibiting the most severe lung disease showed the least benefit from this treatment, and Dr. Alton hypothesizes that fibrosis and mucous barriers associated with more severe lung disease could be obstructing the interaction with lung tissue--preventing the transfer of the healthy gene.

Dr. Alton believes that this study, while modest in benefit, provides proof of concept that gene therapy should be further developed as a tool for treating CF.  The next steps would involve pushing the boundaries to see if further benefit might be obtained with higher dosages.  Also, if gene therapy is able to activate a small amount of CFTR in the lungs, there is the possibility that the chloride transport by this small amount of CFTR could be enhanced with the addition of a small molecule potentiator such as Kalydeco.

While gene therapy is an exciting concept, it is something that researchers have been working on for decades--basically since the discovery of the CF gene in 1989.  The treatment benefits seen in the trial were modest, but represent the greatest success to date using this approach.  Dr. Alton seems determined to continue down this road, but I have doubts... Personally, I think that the gene-editing or mRNA editing techniques (such as CRISPR-cas9 that we will hear about later in the conference) hold more promise as a way of actually changing an individual's genetic expression.  Just my opinion.  I was hoping for much better data after so many years of development.

Mesenchymal Stem Cell LL-37 in Cystic Fibrosis.  Presented by Tracey Bonfield

Human mesenchymal stem cells (hMSCs) come from bone marrow, and are able to differentiate and develop into many different cell types in the body.  There is no need to suppress the immune system to utilize hMSCs, making them an attractive candidate for therapy development.  

For this study, the CF mouse model was used to test how hMSCs might affect CF lungs.  The mice were infected with Pseudomonas aeruuginosa and then treated with hMSCs.  The mice were followed for 10 days.  The data collected suggests that hMSCs exhibit both anti-inflammatory as well as anti-microbial properties.  The rate of Pa growth in the mice was decreased, and combination with an antibiotic treatment produced a synergistic effect (augmented the potency of the antibiotic).  

While this work is preliminary, this trial in mice shows measurable benefit, and further studies with hMSCs to treat CF lungs will be coming our way in the future.

Hormone Fluctuations Correlate with Respiratory Symptoms in Patients with Cystic Fibrosis. Presented by Raksha Jain.

Existing data has suggested that women with CF have worse health outcomes than men. Women demonstrate earlier colonization with respiratory pathogens and an increased exacerbation rate near ovulation.  This study examined the role that sex hormones play in CF.  

This was an observational study where hormones were measured throughout the course of the menstrual cycle.  Inflammatory markers were measured, and patient reported data was collected as well.  Additionally, data was collected for women with CF who were asked to cycle on and off birth control pills--which function as an estrogen inhibitor.

The data they collected basically suggests that higher estrogen levels correlate to worse respiratory symptoms.  This was shown with an increased rate of exacerbation during the follicular phase of the menstrual cycle (when estrogen is highest).  It was also shown that suppression of estrogen with oral contraceptives trends toward reduced exacerbations, and should potentially be examined as a therapeutic option (this was a very small study, so these findings are suggestive rather than conclusive). 

The take-away message--further study is warranted to determine if oral birth control pills may represent a way to improve the health status of women with CF through the suppression of estrogen.  

These 3 studies represent a tiny fraction of the discussions I saw today (I didn't even make it to my afternoon notes yet--but I have to be able to stay awake tomorrow)!  

After the morning session concluded at NACFC, Brock and I dashed over to the Volunteer Engagement Conference at the Renaissance to snag some lunch and connect with other CF families. I also had the privilege to speak about advocacy alongside Mary Dwight and Abi Green from the CFF, and my CFF National Advocacy co-chair Melissa Shiffman (who filmed an awesome advocacy video that I will be able to share when the link is made available).  Nothing inspires me to preach advocacy like spending my morning listening to the amazing scientific progress that is happening RIGHT NOW. 
I made it on and off stage without falling on my face--success!

 It makes me sick to my stomach to think about struggling with access barriers when we have so many wonderful opportunities speeding through the drug development pipeline.  I feel strongly that advocacy needs to be a priority for anyone who cares about the future of someone with CF, because progress means absolutely nothing in the absence of access.  I love analogies, and in my mind, we--the CF community-- are all piled in this homespun machine, moving closer and closer to the finish line (curing CF).  

Inside our machine are multiple interlocking gears that must mesh and spin simultaneously.  The awareness gear interacts with, and helps power fundraising--which leads to scientific investments--which ultimately bring new drugs and therapies into existence.  

The engine of our machine is humming along at breakneck speed!  BUT, there is another crucial juncture we must attend to, where all our inner gears interact with the axle (the ADVOCACY gear). This is the gear responsible for physically spinning the wheels to propel us forward.  If we fail to make that interaction with our system, our inner gears will be left to simply spin...while our machine goes NOWHERE.

You can imagine that it wouldn't take very long for those spinning wheels (and impatient families) to build up some intense heat.    

I believe that we MUST advocate to avoid a situation where the inner gears of our machine are held back by a structure that isn't ready/willing/capable to help us move those wheels closer to our goal. Imagine for a second that advocates HADN'T recently been successful at passing the Ensuring Access to Clinical Trials Act (EACT), and we had the money and science to move forward with exciting clinical trials--but barriers to trial participation stood in our way and slowed us down... I know that I would get hot under the collar in a hurry.  Knowing the passionately CF community the way that I do, I think we run the risk of some serious engine trouble in that situation. We can't let that happen.  

Advocate regularly to avoid engine trouble!
With that, I will close for tonight.  Tomorrow is another full day of worshops and symposium sessions.  Plus, I need to be at my best for lunch with Dr. Beall, and dinner with some of the best scientists in the world.  Stay tuned--we are just getting started!

Thursday, October 8, 2015

Welcome to NACFC 2015

The North American Cystic Fibrosis Conference brings together thousands of brilliant scientists and clinicians to discuss their research, and ways to improve care in CF clinic.  As a CF Mom with a chemistry degree, I am drawn like a magnet. The conference is draining--physically, intellectually, and emotionally.  I subsist mostly on coffee, wine, and protein bars and don't sleep much.  I am a zombie by the time I get home, and my head spins for weeks on all the new information I have learned, and people I have met...and I wouldn't miss it for the world!  I even attended in 2012 on crutches after knee surgery.  It would take a natural disaster of some kind to keep me away.

This year, there is a new event piggybacked on the NACFC called the “Volunteer Engagement Conference (VEC), which will bring volunteers from the West together for scientific updates and Foundation news.  My husband and I arrived in Phoenix yesterday afternoon and attended a beautiful welcome reception for volunteers and Foundation leadership at the home of Robert and Carole Griego.  It is always really special to me when I get the chance to spend time with other CF families.  I’m excited to speak at the VEC this afternoon about the importance of prioritizing advocacy as we move through an evolving healthcare system toward personalized treatments for cystic fibrosis.   

As you can imagine, there is a mountain of new scientific information to digest every year.  I have every expectation that this year is going to BLOW MY MIND.  This morning, my plan is to attend the workshop entitled “New Advances in CF Animal Models.”  I’m going to send my husband Brock to the “Novel Targets and Outcome Measures” workshop to take notes and pictures.  I hope to have another post later today about what we learned.  After lunch, I will be speaking at the Volunteer Engagement Conference alongside Mary Dwight and Abi Green from the Foundation, and my National Advocacy co-chair Melissa Shiffman.

This afternoon, I will be attending a symposium-- “Partnering with Patients and Families to Promote Healthy Lifestyles,” which will feature discussion about exercise, alternative therapies, anxiety management, and wellness through diet.  After that, we will attend the first Plenary session—“Personalized Medicine,” where several speakers will discuss the process of tailoring the care and drug regimen to the needs/mutations of each individual patient.   

It is such an awesome feeling to sit in the huge room where the Plenary sessions are held--surrounded by 4000+ professionals who all care deeply about curing CF.  It is like being transported to another planet where, fortunately, I speak the same language as the natives.  

I’m a little nervous about my knee brace/high heel combo, so hopefully I don’t take a nose dive down the escalator! Barring disaster, I will be blogging to the best of my ability again this year.  Stay tuned for updates!

Monday, March 23, 2015

Come to the Table

I hate politics.  I really do.  I haven't taken a political science course since Freshman year.  All the partisan bickering and lack of action on important issues is annoying and frustrating.  It often seems like campaigning for the next election is all many of our politicians care about, and I can’t stand to watch live television during an election cycle because it makes me want to throw things at my TV…
So why in the world would I travel from northern Idaho to Washington D.C., suit up, and walk 8 miles in heels navigating the maze of offices on Capitol Hill?  Why do I feel absolutely compelled to inject myself into that political world and lob my heart onto the lovely mahogany desks of my elected representatives?   Because I am a mother of a child with cystic fibrosis.  For me, this is not political—this is personal. 

Brady is 7 years old, and LEGO obsessed!  Sometimes it feels like my whole world looks like this!
Whether we like it or not, our healthcare system is evolving, and every year lawmakers are voting on legislation and budgets that will directly impact families and patients living with cystic fibrosis.  The Cystic Fibrosis Foundation understands this, and has been working to establish a presence on Capitol Hill for many years.  On March 19, over 120 CF advocates, representing 38 states participated in 273 meetings in the CF Foundation’s “March on the Hill” event.    This is an opportunity for CF experts (YOU!) to come to the table, and educate elected officials on what it means to live with cystic fibrosis.  It is our opportunity to bring the unique needs of our community to their attention, and explain how budget appropriations and certain pieces of legislation can impact those living with CF.  Not convinced this is for you?  Let me outline the ways that CF advocacy has touched my own life.

July 26th 2007, Brady came into this world.  He was the first baby in Idaho to be picked up on the newborn screening program.  That test was added to the newborn panel in Idaho the same week that Brady was born.  After a positive screen came back, we performed genetic testing and he was diagnosed with CF before he was 3 weeks old.  We were able to intervene immediately, and begin treatment with enzymes, airway clearance, CF vitamins, and other medicines that would help him grow and thrive.  He didn’t have to become terribly ill and suffer potentially irreversible damage before we knew something was wrong.  Obviously, the diagnosis was traumatic (especially in the throes of post-partum sleep deprivation and fluctuating hormones), but the benefits of early intervention are well studied, and we are eternally grateful that we had the opportunity to begin helping Brady fight this disease as soon as we could.  The newborn screening program is up and running in all 50 states, which is awesome!   Newborn screening exists today because CF advocates worked for years on Capitol Hill to get it added to the newborn panel in each and every state. 

When Brady was a baby, I learned that the Idaho Legislature was proposing legislation to cut a co-pay assistance program for adult patients with CF. The budget for this program was a mere drop in the bucket ($200,000 total annual budget), but a game-changer for adults needing assistance in Idaho.  We already know that 1 in 4 CF patients sometimes skip doses of medication, or go without some prescriptions all together because of cost issues.  Cutting this program would mean that many adults with CF in my state would lose the ability to get some of the drugs that they needed to manage their disease.  It made $1000+ co-pays a monthly reality for many adult patients in Idaho.  It caused severe anxiety and depression for some of those adults already struggling with advanced disease.  It caused some adults who had previously been able to work part-time to lose/quit their jobs and become fully dependent on Medicaid or SSI for coverage of their life-sustaining drugs.  It sucked (especially when I learned that the Idaho Legislature was creating a new “slush fund” with a $200,000 annual budget to pay lawyer fees when legislators found themselves in lawsuits that same year).  Everything about it reeked.  Though it wouldn’t affect Brady directly (the program was for adults only), he was on a similar state program for children, and I realized that lawmakers were going to be making decision about his access to care and drugs.  I realized that many of the people making those decisions didn’t even know what cystic fibrosis was.  I realized that unless I spoke up—they may never know.  (Insert long rant of obscene language, and imagine me banging my head against a brick wall).

A newspaper article from our battle with the Idaho Legislature.

If you are reading this blog, you might already know that my son Brady has been taking Kalydeco for over 3 years, and that it has changed our lives.  But did you know that the technology that led to the discovery of Kalydeco—“high-throughput screening,” was developed by the National Institutes of Health?  Did you know that targeting a genetic mutation for correction wouldn’t be possible without the NIH first mapping the human genome?  Without the basic science that has helped us unravel the mysteries of our DNA, we wouldn’t even be able to DREAM of the kinds of “genetic modifying” drugs like Kalydeco that are being crafted today.  Just to be clear—the CF Foundation funds nearly 100% of medical research for CF.  The National Institutes of Health does NOT give a single dollar to the CF Foundation, or “orphan” (rare) disease research.  They DO, however, fund basic science projects that enhance our understanding of genetics.  They DO develop new technologies that could accelerate drug discovery for all diseases.  They DO fund generalized research projects that may eventually be applicable to CF.  The importance of funding the NIH has ALWAYS been a priority for CF advocates.

Take a look at our drug development pipeline.  It is jam packed with hopes and dreams.  Hopefully, many of the drugs in clinical trials right now will be applying to the FDA for review in the coming years.  When new drug applications are submitted, it is vitally important that the FDA has the resources they need to expertly and swiftly review those applications.  The CF Foundation has worked for many years to build a relationship with the FDA, and enhance their understanding of our projects and goals.  Kalydeco was granted “priority review” status by the FDA, which served to expedite the approval process, and was given one of the fastest reviews in history (less than 3 months from submission to approval!)  Awesome! As you know, the  quicker these miracles can get into patient hands…the better. 

I hope I've made my case that CF advocacy is not about politics after all.  I honestly believe that working to help shape our system is the most important way to ensure progress toward the cure and protect Brady's access to care and medicine.  After attending the NACFC for the last 4 years, I am amazed and inspired by the science coming through the pipeline.  We don't want roadblocks on the path to the cure. It is extremely important to educate our lawmakers on the unique needs of the cystic fibrosis community if we want a system that helps individuals and families with CF thrive... and YOU are the best experts in the world! It is much better to proactively troubleshoot problems that we foresee as we move toward the cure, than sit back and complain about a system that doesn't work for us when the damage is already done.  CF advocacy is about coming to the table and giving input about the policies that are shaping the future of healthcare,  With that in mind, I want to share more about the specific action items that March on the Hill advocates met with lawmakers about last week. 

1) Co-sponsorship of the Ensuring Access to Clinical Trials Act of 2015 (EACT) S139 H.R. 209
This legislation removes the sunset provision (expiration date) from the "Improving Access to Clinical Trials Act" (IACT), which was passed in 2010.  IACT allows patients with CF and other rare diseases to receive up to $2,000 in compensation for participating in clinical trials without that compensation counting toward their income eligibility limits for SSI and Medicaid.  Without this legislation, patients that we NEED to be able to participate in clinical trials, may not be able to, out of fear of losing their vital benefits.  The Cystic Fibrosis Foundation is planning to fund 18 clinical trials next year--requiring 2500 patients to participate.  When you consider the various exclusion criteria for those trials, and the fact that we only have about 30,000 CF patients nationwide--it is extremely important to remove this barrier to participation.  IACT is set to expire in October.  Advocates are trying to get EACT passed before this happens!  This legislation costs a negligible amount of money, but is extremely important to ensure speedy and full enrollment of new clinical trials.  EACT applies to all rare diseases, not just CF.  Rare diseases impact nearly 1 in 10 Americans.  According to the NIH, there are over 7,000 rare diseases affecting between 25-30 million people across the country.  Rare disease researchers face real challenges recruiting enough patients to perform trials, and current treatment options are often very limited.  Back in 2010, IACT received bipartisan support, and has allowed us to progress quickly forward with trial enrollment for the last 5 years.  We really aren't asking for anything new at all with EACT--simply to remove the 5 year expiration date, and allow the law to remain permanent.  Last week at March on the Hill, CF advocates from 38 states attended 273 meetings--and asking for support of this legislation was a priority in every one.  EACT also has good bipartisan support...but we need to push it across the finish line here and now.  You can help by taking action through the CF Foundation's advocacy page.  Click, "Take Action Now," then "Tell Congress to Protect Access to Clinical Trials," and follow the prompts.  You can personalize the pre-written letter a bit with your CF connection, and send it directly to your representatives!  This takes about 1 minute, and is a really effective way to let lawmakers hear your voice!  It would be especially helpful if constituents from Texas could help us put some pressure on Senator Ted Cruz.  I mean, the CF Foundation is funding the research.  All we want is the opportunity to test our new amazing science in clinical trials! Is that too much to ask?  NO!

2) Support funding for the NIH and FDA.  
CF advocates are working to boost funding to the NIH this year and are asking lawmakers to approve a budget where the NIH receives at least $32 billion dollars in 2016. NIH funding has been flat since 2002 (which translates to a DECREASE in funding each year when you take inflation into account).   That means that the NIH has been able to fund fewer and fewer interesting projects that are seeking funding each year.  What is slipping through our fingers in those missed opportunities?  What if one of those basic science projects might lead us to a cure for CF?  It requires you to take a big step back and take a look at the big picture, but we NEED to see basic science research take a bigger priority in our government’s budget appropriations.  Globally, America is falling behind, and it is only going to get worse unless we change this trend.  Investing in medical science is an investment in the FUTURE of this country, and the future of our loved ones with CF.  Last week, CF advocates explained why NIH funding is important to the CF community on Capitol Hill, and asked them to sign the "Dear Colleage" letter circulating in both the House and the Senate to show their support of the $32 billion dollar budget.  You can "Take Action Now," then click "Protect our Progress Toward a Cure for CF," and follow the prompts.  Once again--a minute of your time could make a big impact for families living with CF.  

The FDA worked smoothly and quickly for Kalydeco.  Why are we making FDA funding an issue?  The medical research community is soon going to be asking the FDA to consider a huge number of new drugs in different ways than it ever has before.  Historically, to be considered a candidate for approval, the FDA has required long term trials with a large pool of patients.  Obviously, these criteria aren’t going to work for mutation specific CF drug trials.  As a rare disease, and with new therapies targeted at specific genetic mutations, there may only be a few hundred (or less) “qualified” patients that even exist worldwide!  It would be impossible to enroll huge numbers of patients for individualized genetic treatments for an already rare disease.  In 2012, CF advocates played an integral role in the passage of the EXPERRT Act.  As part of this legislation, a new “breakthrough” designation was created for drugs that treat life-threatening diseases, for which there is no alternative.  Drugs that are granted breakthrough status, are given a faster review schedule than ever before.  The legislation also enables the FDA to bring in disease experts to consult on trials that don’t fit the old school criteria.   Passage of the EXPERRT act was a big victory for the CF community, but we aren’t satisfied yet.  While CF is blazing the trail for this type of drug design, an increasing number of disease communities are uncovering genetic correlations of their own, and developing targeted therapies.  Personalized treatment is the future of medicine for everything from CF to cancer and beyond.  The FDA is going to need a larger staff to effectively review the growing number of new individualized drug applications coming their way in the near future.  What a shame it would be to see amazing new drugs bogged down in delays over a simple lack of time and personnel to perform safe and prompt reviews.  We want our future new drug applications to be considered with the same prompt expertise we saw with the Kalydeco approval.  Bottom line is that the FDA is going to need more money to function like we need it to in the very near future. If you sent the "Protect our Progress Toward a Cure for CF" email, you are already done!  Robust funding for both the NIH and FDA are included in that request!

3) Join CF Caucus in the House of Representatives.  

The CF Caucus is sort of like a "club" that House Representatives can join to signify their support for the CF community.  Follow the link to see if the people who represent you are members! Membership in the caucus raises awareness about CF, and issues that will impact patients and families living with the disease.  We try to grow membership in this Caucus every year. Currently, there is no CF Caucus in the Senate.  We don't have a specific action item in our CFF advocacy toolkit for this, but you are always free to email your own elected State officials and invite them to join the CF Caucus in the House (or find a great supportive Senator to START a caucus in the Senate!).  

New issues come up all the time that could affect the CF community.  To me, advocacy is about putting face on this disease, and letting our lawmakers know that their votes affect us as people.  We are not just a number in a budget.  Their votes mean something to us.  We are the Mothers, Fathers, Grandparents, Sons, Daughters, Brothers, Sisters, Aunts, Uncles, Friends, and Patients dealing with this disease.  As despicable as politics can seem at times...our lawmakers are actually just people.  Most of them have families, and can imagine what dealing with CF must be like.  I try to relate to them on a personal level to help them understand.  When you are sitting face to face with them, the intimidation fades away, and it becomes apparent that they are actually very much like us. I encourage you to explore CF advocacy efforts in your state, and contact with questions.  

As a mother who has been lucky enough to see what a bright future new therapies like Kalydeco might hold for our CF community, I am determined to remove system barriers that might slow us down. I want EVERY patient and family to have a miracle like Kalydeco! I am honored and excited to serve as the CF Foundation's new National Advocacy Co-Chair with an awesome lady, Melissa Shiffman from NY.  Melissa is an adult with CF, who is the mother of two beautiful children.  As we are moving toward the goal of curing CF, there WILL BE OBSTACLES that require advocates to speak up.  I believe with all my heart that if we want a system that works for us...If we want coverage that meets our needs...if we want to be fed...we must first come to the table!  My life has been so touched by CF advocates.  I feel like "Thank you" is a huge understatement.  Besides, once you get bit by the advocacy bug, you can never quit!  It is so empowering!  Get involved in advocacy today and help protect the future for everyone with CF. Please "Sign up" to receive the CF Foundation's advocacy newsletter, and action alerts!  How about taking 30 seconds to advocate for CF patients RIGHT NOW by sending a tweet to Senator Ted Cruz in Texas asking him to support EACT?!  Something like...

"The ‪#‎CysticFibrosis‬ community needs access to clinical trials, @SenTedCruz Pass S. 139!! ‪#‎cfAdvocacy‬ @CF_Foundation"

Thank you wonderful people!  

With my RAD new Co-Chair Melissa Shiffman on Capitol Hill last week!

Chatting up CF advocacy at Sacred Heart's Family Ed day a few weeks ago. Do I ever shut-up?  NOPE!
And neither should you!


Tuesday, October 14, 2014

The KIWI study:Ivacaftor for 2-5 year olds

I know that many of you have been anticipating this information.  It wasn't presented until 4:00 p.m. on Saturday, and I apologize for the delay...

An Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Patients Aged 2 to 5 Years With CF and a CFTR Gating Mutation: The KIWI Study
Jane Davies

Early intervention with a CFTR modifier like Kalydeco holds exciting potential. The hope is that the progressive organ damage associated with cystic fibrosis could be PREVENTED by early treatment. 

The study was designed mainly to assess the safety of  Kalydeco.  Patients were given either 50 mg. or 75 mg.(for patients over 14 kilos) Ivacaftor twice daily, in a newly designed granular powder formulation.  The trial was not placebo controlled--all participants received the real drug.

While the study was open to children with any of the approved mutations listed on the slide below, the vast majority were enrolled with G551D.

Investigators collected data on pharmacokinetics, safety, sweat chloride, weight, BMI, Z-score, Fecal elastase-1 (measure of pancreatic function), Immunoreactive trypsinogen, and for the few kids in this age group that could reliably perform spirometry--FEV1. The majority of kids were unable to perform spirometry with good enough technique to be considered a valid measure.

You may recall that FEV1 was the primary endpoint in Ivacaftor trials in older kids and adults with CF.  This trial was focused more on the safety of the drug in the younger group, and the utility of the new granular formula of administration.

The most notable adverse events reported in the study were the 5 patients that experienced increased liver enzymes during the Kalydeco trial (>8X normal levels).  3 of those patients chose to ultimately withdraw from the study.  The speaker noted that all 5 of these patients entered the study with mild liver impairment.  The speaker also commented on the wide number of health factors that can lead to increases in liver enzymes such as: illness, vaccinations, other medication such as antibiotics... Liver enzymes monitoring is recommended for everyone taking Kalydeco, and this group is no exception.  During the question/answer period of the discussion, someone asked about the "high rates" of vomiting reported.  I actually found myself laughing a bit at this question...because 2-5 year old kids vomit a lot, whether they have CF or not.  Kids in this age group are fairly notorious for teething, getting viruses, not chewing up their food well enough, or the thousand other reasons they might find to puke.  The investigator seemed to be thinking along the same basic lines, and felt that if a placebo arm of the study had existed, similar rates of vomiting would have presented.  No opthomological effects (cataracts) were observed.

Researchers were astonished to discover the pancreatic function improvements in these patients, as witnessed in fecal elastase examination.  An audience member asked if patients were able to reduce or stop enzymes, and the speaker responded that they had not been instructed to, but she had heard that some patients had.  Another person asked about the potential to increase the risk of pancreatitis by giving patients "partial pancreatic function."  The speaker responded that she couldn't really answer that question (because she didn't know), but that there was no evidence of those issues in the clinical trial period. Investigators were also surprised to see changes in IRT levels, and weren't exactly sure what the clinical implications of these changes might be.  

I am extremely excited to see Kalydeco reach this younger population group.  If you follow my blog, you probably already know how strongly I believe in early intervention with CFTR modifiers to PREVENT the organ damage associated with cystic fibrosis, and enable these individuals to live longer, healthier, and more productive lives than ever before...

In closing, I want to share this testimony that I just sent to the FDA.  They are currently reviewing the application of Kalydeco for R117H. There is plenty of evidence that Kalydeco works to restore CFTR function for this mutation, but R117H is typically considered a "milder" mutation of CF. These individuals don't often present with serious lung disease until later in life, and did not show the same level of statistical FEV1 improvement in clinical trials.  I feel strongly that people shouldn't have to get sicker, as the only means to make themselves eligible to become well.  It just doesn't make sense. I want to see EVERY PATIENT THAT CAN BENEFIT, whether you are a 2 year old with G551D, or a 30 year old with R117H, have access to Kalydeco.  I want to see patients prevent damage with this drug and enhance the quality of their lives.  I encourage anyone who has experience with Kalydeco, or who has R117H to submit testimony of their own.  I also hope that parents of children 2-5 with approved gating mutations are poised and ready to make similar arguments in the coming weeks if testimony is requested as part of the FDA review process.   Submissions for R117H should be sent to Cindy Hong: by October 16th.  This is what I said:

My name is Rebecca Schroeder, and I have a 7 year old with cystic fibrosis named Brady.  Brady started taking Kalydeco on February 10th, 2012, at the age of 4 1/2.  Though he had maintained his lung health fairly well up until that point in time, he still spent approximately 2 hours a day on breathing and airway clearance treatments to maintain that function.  He also suffered from the classic pancreatic insufficiency associated with CF, which caused him considerable discomfort in the form of digestive dysfunction.  For Brady, cystic fibrosis also brought serious upper respiratory inflammation that manifested as sinus polyps. A CT scan revealed that the polyps were growing so aggressively, that they had begun to thin and shift the fragile bones in his face--and threatened to break through his eye socket, leading to possible blindness or brain damage.  Brady had absolutely zero sense of smell.  He underwent sinus surgeries as a 4 year old before beginning Kalydeco, and took frequent bursts of oral Prednisone, performed 3X daily steroid/antibiotic sinus rinses in an attempt to control the swelling.  Quality of life was poor, to say the least.  We did everything we could to battle the progression of the disease, but the symptoms he suffered through everyday made all of our lives hell, despite our best efforts.  Watching your child struggle to breathe is an indescribable torture.  

Everything changed the day Kalydeco arrived at our door.  Within a few days of beginning therapy, we began to see Brady's health completely transform.  As the committee is likely aware, Kalydeco treats cystic fibrosis at the root cause of disease, by restoring CFTR protein function to all the affected organs in the body--lungs, pancreas, sinuses, and the entire gut.  Almost overnight, the serious sinus polyps that Brady had battled on a daily basis for YEARS began to recede, and he discovered his sense of smell for the first time, in a long time.  Before Kalydeco, his sinuses were completely blocked.  I heard every breath he struggled through at night, because his bedroom is right next to mine.  He would frequently snore/snort himself awake during this struggle, making restful sleep impossible.  After 3 days of Kalydeco, all the awful sounds coming from his room stopped.  Brady's breathing became so effortless and silent, and he slept so soundly--that it scared me to death!  My husband and I found ourselves running into his room several times, every single night, to ensure that he was still breathing at all.  The change was truly remarkable. In the 6 months before beginning Kalydeco, Brady had seen his Ear/Nose/Throat specialist 11 times.  Post-Kalydeco, he has only seen that Dr. ONCE--to document the complete disappearance of symptoms.  Additionally, we observed that Brady's energy level shot through the roof, his digestive function improved dramatically, and the constant stomachaches disappeared.  He began to grow and gain weight beyond our wildest dreams.  He began to smile more.  Furthermore, the mucus in Brady's lungs became thin and watery, rather than thick and sticky as it had been before.  The mucus began to function as the vital organ lubricant it was designed to be, and has maintained his lungs FREE from the invading organisms associated with CF mortality.  His CT scan shows that he is FREE of bronchiectasis (irreversible widening and loss of elasticity of the airways).  Brady is now FREE from the hours of daily breathing treatments he used to rely on as ammunition in a losing battle... Today, Brady has those two hours he used to spend doing breathing treatments each day to simply play, and just be a kid. Because Brady hadn't suffered excessive lung damage when this miracle drug was added to his regimen, he no longer has to face an inevitable future of progressive lung disease. I don't EVER anticipate having to face the painful prospect of a double lung transplant, which is unfortunately, the only way to extend life for most individuals with CF.  

I feel that I am in a unique position to provide valuable testimony to the board considering Kalydedo for approval for the R117H mutation.  I have attended the North American Cystic Fibrosis Conference for the last 4 years, and seen proof that Kalydeco works to restore CFTR protein function for this mutation.  R117H is considered one of the "milder" CF mutations, which means that serious lung disease often doesn't present until later in life.  These patients ultimately still suffer the same fate as other mutations that have already have access to Kalydeco, like G551D--but the later onset of symptoms provides an ideal window of opportunity for intervention in disease progression.  I contend that the statistical improvements in FEV1 were smaller for this group of patients, because their lung function was higher to begin with.  Lung function must first be lost, in order to make those gains possible.  If large jumps in FEV1 are the main criteria for approving a disease altering therapy like Kalydeco--many of the patients that stand to benefit MOST, will be excluded.  Patients like Brady, who could represent the first generation of individuals to LIVE a normal life, and successfully manage the symptoms of CF would be denied their miracle.  If you took Brady to the lab today, and performed the sweat test on him--a diagnostic test which is correlated to CFTR function--he would test negative for cystic fibrosis.  The drug has changed the way his body functions on a fundamental level, and will likely add decades of time, and immeasurable quality to his life.  I urge you to consider the implications of denying patients this drug in the abcense of a larger jump in FEV1.  That requirement is akin to demanding that these patients first become more ill, before they are eligible to become well. One thing is for sure, if you wait long enough, the damage is guaranteed to happen in CF.  With the median life expectancy hovering around 40 years old, time is not a luxury we enjoy in this community. 
I beg you to examine the evidence on Kalydeco's powerful impact on CFTR function for this group, as well as the additional positive outcomes I have detailed.  After seeing the positive effects of this drug in my own child, the thought of delaying or denying access to R117H patients is unconscionable.  I am desperate to see this remarkable innovation reach R117H patients.  Kalydeco would help these individuals, and could make them part of this new generation, who easily outlive their parents.
Thank you so much for your time and consideration.  Sincerely,
Rebecca Schroeder

Sunday, October 12, 2014

Beyond Small Molecules--Gene Editing Strategies Provide Real Hope to Truly "Leave No Mutation Behind." NACFC 2014

Successful rescue of CFTR function with small molecules like Kalydeco, or corrector/potentiator combination therapies (VX-809/VX-770) hold a lot of promise for the immediate future of altering the course of CF disease.  The tricky part about small molecule therapy, is that different mutations produce their own unique issues.  As we know already, Kalydeco monotherapy is effective for a small percentage of CF mutations, but produces little or no effect at all, in others.  Finding novel combinations of correctors and potentiators to successfully rescue robust amount of CFTR protein function for the myriad of mutations will not be a simple task.  Each year, I hear about dozens of new corrector and potentiator compounds that may be combined in different ways to successfully affect CFTR rescue.  After seeing the potential of this type of therapy in my own son, I am anxious to see more small molecules treatments successfully reach the market.

The small molecule approach can be a very powerful way to impact CFTR function, but still represents a temporary fix for a permanent problem.  For patients like Brady, Kalydeco might be considered a "one day cure."  As long as he maintains sufficient levels of Ivacaftor pumping through his veins, his body doesn't really realize it has CF..., BUT, if he were to stop swallowing those expensive little blue darlings, his CF symptoms would return quickly.  Because of the temporary nature of the effects, small molecules don't really fit the bill as a true cure.  While the CFF has millions of dollars invested in the development of new small molecules, they are also looking even further toward the future. Ultimately, we would all love to see a LIFETIME cure, rather than a ONE DAY cure.  True to the "venture philanthropy" model that The CF Foundation has made famous, they are poised to make considerable investments in new exciting fields of research that could yield that lifetime cure that we all dream of, for each and every person with cystic fibrosis--regardless of their genetic mutations.  I was disappointed that the UK Gene Therapy Trial results were not presented at this meeting as scheduled, but there are plenty of other new technologies to get REALLY excited about.

Symposium Session 8: Gene Editing Strategies for Therapy and Research

In this session, two technologies were described to manipulate genes such as CFTR. What makes these techniques so attractive is that they have the potential to be tailored to treat diverse cystic fibrosis mutations. These techniques can be thought of as "mutation agnostic," and could provide functional results for the multitudes of CF mutations, no matter how rare or complex the dysfunction.

1) Genome editing by the CRISPR/Cas9 system
2) RNA editing--where mutations in messenger RNA are corrected without modification of the genomic DNA

Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of CF Patients
Jeffrey Beekman

To perform this study, adult intestinal stem cells were obtained from rectal biopsies of adults with CF.  Just to be perfectly clear--embryonic stem cells were not required in this research.  The tissue samples obtained from the rectal biopsies were then taken into the lab, where they were manipulated to create intestinal organoids for experimentation.  Most people have heard a lot about changes in sweat chloride levels as a measure of CFTR function.  Over the last several years, I've seen more and more evidence that, while correlated with CFTR function, sweat chloride levels may not paint the most accurate picture of how much functional CFTR is being rescued.  A better way to directly measure CFTR channel function is to examine intestinal organoid swelling.  

This slide details the methods used to grow organoids from adult stem cells. 

CFTR function can be directly measured via the amount of swelling that intestinal organoid cells exhibit.  The amount of swelling can be directly correlated to CFTR function.  This has been found to be a much more accurate measure of CFTR channel activity than sweat chloride measurements.

 For the record, CRISPR stands for clustered regularly interspaced short palindromic repeats--specific targets on a gene, containing short repetitions of base sequences, followed by short segments of "spacer" DNA. Cas9 is a single DNA targeting enzyme that serves to "code" for proteins related to CRISPRS.  In simpler terms, the CRISPR can be thought of as the specific portion of DNA targeted for alteration (the section where we find the presence of the CF mutation).  Cas9 can be thought of as a tiny pair of scissors, programmed to make a cut in the strand of DNA at precisely the right spot.

Here, the CRISPR-Cas9 gene editing system was used to repair the CFTR-F508 target.  Once the double strand cut is made in the DNA by Cas9, the DNA undergoes homologous recombination--or automatic repair to "fix" the break. After recombination, the repaired DNA no longer contains the problematic CF mutation.

Using this method, researchers were able to restore functional swelling of the organoids in homozygous DF508, indicating restored CFTR function.

This work is very preliminary...but extremely exciting.  This experiment serves as proof-of-concept for "regenerative medicine" approaches of CF using gene-corrected adult stem cells.  In addition, this study shows that intestinal organoid swelling can be an effective mode of measuring CFTR function for future studies.  At this point, researchers will need to work on improving the efficiency of correction, which is still very low.  They seem confident that refinement of technique can produce much higher efficiency in future studies.

Correction of Genetic Mutations By Site-Directed RNA Editing
Joshua Rosenthal

The description of RNA editing involves a lot of technical jargon, so I am going to lay this out in two totally different ways—first the scientific version, and then my layman’s translation. 

Version 1:
Adenosine deaminases that act on RNA (ADARS) are a family of enzymes whose activity resembles a natural form of targeted mutagenesis.  Biochemically, ADARS convert adensosine to inosine—a nucleotide that is read as guanosine during translation.  ADARS are modular enzymes with distinct domains that perform different functions.  At one terminus, they contain a deaminase domain that catalyzes the deamination of adenosine to inosine.  At the other end, a number of double-stranded RNA binding motifs (dsRBMs) are found.  These dsRBMs bind to the tertiary structures in pre-mRNAs.  It is problematic to manipulate the ADARS targeting mechanism, so researchers decided to replace ADAR’s dsRBMs (the binding end of the enzyme) with a more easily manipulated, antisense RNA oligonucleotide—which could be easily directed to bind with any primary sequence along an RNA.  Researchers found, that when this antisense RNA oligonucleotide was joined with the dsRBM (via a small bacteriophage binding protein), they could selectively target and edit a single adenosine.  When editing occurs in mRNAs, codons can be recoded and the changes can alter the protein function.  For example, mutations which cause premature termination codons (UAA, UGA, UAG) could be recoded to tryptophan (UGG) to achieve successful protein read-through.  To test their editing system, and provide proof of concept for encoding CFTR, researchers selected the W496X mutation, which contains an early “stop” codon.  In vitro, they showed that their system of directed editing could correct W496X with near perfect efficiency.  In Xenopus oocytes, the genetically encoded version of their editase corrected CFTR mRNA, restored full-length protein, and reestablished functional chloride currents across the plasma membrane.  In human cell lines (grown in lab), their editing system was able to correct a non-functional version of enhanced green fluorescent protein (eGFP) with a premature termination codon.  The next step is to try and correct endogenous CFTR W496X, and other CFTR mutations caused by G-to-A transition, in epithelial cell lines. 

Version 2:
Since I am sitting in the airport, I will also describe RNA editing like this—Imagine DNA as our flight map.  This “map” tells the pilot what the final destination is, and how to get there.  The RNA can be thought of as the “pilot” of our flight, whose job is to follow the map, and deliver passengers where they are supposed to go.  Of course, the pilot (RNA) knows all the details about the trip: how high to take the plane, when to make turns, and how to land at the final destination.  The problem is that sometimes the pilot shows up drunk, and causes the flight to crash and burn.  In that case (as with premature stop codon CFTR mutations), none of the passengers reach their destination.  ADARS (paired with the antisense RNA oligonucleotide) can be thought of as “hijackers,” secretly coming onboard and forcefully changing the details of the flight plan.  They mask the pilot, steal his uniform, pilot hat, and cute little wings (to look “official” and keep the passengers calm) and take the plane to a different destination than originally planned.  Fortunately, the hijackers (in the case of RNA editing) are actually pretty cool (especially compared with to the passed out drunk previously in charge), and instead of taking the blissfully unaware passengers to their originally scheduled work conference in Shittsville, (no CFTR protein produced) decide to redirect the flight to an all-inclusive resort in The Cayman Islands (functional, full-length CFTR). 
I hope I was able to convey the fundamental concept behind this new research, because site directed RNA editing is truly a very promising and exciting strategy to correct a broad variety of genetic mutations, in both CFTR as well as other proteins.  The correction of genetic mutations at the mRNA level is attractive for several reasons. 

1) Compared to DNA, mRNA is easily accessible (genomic DNA is sequestered in the nucleus and tightly bound by histones).

2)  Mature mRNA is in the cytoplasm.  The delivery of a site-directed editor to mRNA would only entail crossing a single membrane.

3) Because RNA is transient (where DNA is not), off-target edits (targeting mistakes) are less dangerous.

4) Site-directed RNA editing does not affect mRNA expression level (expression level must be precise—as both under-expression or over-expression can result in disease). 
I've never actually visited The Cayman Islands before...but it seems like a really nice place.

Friday, October 10, 2014

LIVING with CF--updates from NACFC 2014

The NACFC discussions that receive the most attention are typically geared toward the scientific developments.  Obviously, I care deeply about progress toward a cure, but I try to balance those technical talks with some information on ways that we--as a community of patients and families, might be able to have a real positive impact on health through the informed choices we make today.  

The Relationship Between Exercise Capacity and Glucose Tolerance in a Pediatric CF Population Not Diagnosed with Cystic Fibrosis Related Diabetes.
Foster, K.E. Cincinnati Childrens Hospital

Hopefully, most people recognize that regular exercise can provide numerous health benefits to ANYONE.  Regular exercise is especially important for those with CF.  CF related diabetes (CFRD) is a frequently occurring complication of cystic fibrosis, and is associated with greater decline in lung function, poorer nutritional status, and lower life expectancy.  In this discussion, Foster examined the connection between exercise capacity, and the ability to successfully regulate blood sugars.  

Foster measured both exercise capacity, and glucose tolerance (via oral glucose tolerance testing) in 50 patients, and discovered a correlation between low exercise capacity, and increased 2 hour blood glucose values.  This suggests that patients with low exercise capacity have poorer glucose tolerance. Foster speculates that working to improve exercise capacity may help delay the onset of CFRD via improved blood sugar control.  

As you can see in this slide, there isn't hard data on this correlation, but rather, a strong suspicion that blood sugar control may be improved with regular exercise--leading to a delay in the onset of CFRD.  

Since I personally believe strongly in the value of exercise in health maintenance, I want to hammer the point home with one more discussion:

Yoga Improves Posture and Muscular Performance in Adult Persons with Cystic Fibrosis
Scott Russell, University of Southern California

"Persons with cystic fibrosis are prone to posture dysfunction, in part due to pulmonary hyperinflation and chronic coughing which can lead to injury, chronic pain disorders, vertigo, headaches, balance dysfunction, increased risk for vertebral fractures, and loss of physical functioning.  The purpose of this study is to investigate the effects of Hatha yoga on posture, neuromuscular performance, and self-reported psychometric measures."

In this small study, patients agreed to participate in twice weekly, 90 minute, outdoor yoga sessions over the duration of 8 weeks.  A couple of important points worth noting:

1) Strict infection control guidelines were observed--persons with CF were each provided with their own (vs. shared) yoga props, and were equipped with hand sanitizer gel, tissues, etc...  Yoga was also practiced in an open, outdoor area and the "6 ft. rule" was observed due to multiple CF participants in the same class.  Of course, if you decide to take up yoga, it is unlikely that you would be surrounded by other CF patients, and such strict precautions may not be required.  

2) Russell made sure to note that practice of yoga for CF patients often requires modification of poses to avoid the "head down" position, or "inversions," which can aggravate acid reflux/GERD for many patients.  It is very important to educate the instructor about the need for these modifications, since an increase in acid reflux symptoms would be an undesired effect, and could lead to a worsening, rather than an improvement in lung and postural health.

This is hard to read, but it says that the primary aims of this study are to discover 1) the effects of yoga on pulmonary functional, and chest wall mobility, 2) the effects on physical function and posture, and 3) effects on scapulothoracic posture.   Self-reported psychometric measures regarding quality of life were also recorded.  Ultimately, Russell wanted to determine the SAFETY and POTENTIAL BENEFITS of yoga for persons with CF.

These are examples of the "head down" positions that should be AVOIDED if you suffer from acid reflux/GERD.

Here we see an example of a modified downward-facing dog position.  Note that the trunk and head stay parallel to the ground, rather than the typical head down positioning.  A few extra props may be helpful for the appropriate modifications

Russell provided an example of the poses used by the instructor in the intervention.  

The results showed an improvement in chest wall excursion after 8 weeks of the yoga intervention.

Scapular positioning was also improved--positive effects on posture. 

Patients showed improvements in the "Sit to Stand Test" and several other fitness measures.

Patients had improved self-reported attitudes toward their weight/body image.

As I mentioned earlier, this was a small study, but I appreciate that we are discussing topics like this AT ALL, so I wanted to report on it anyway!  It is my blog, and I do what I want! :)

You might even consider doing your own "future investigation" on whether yoga is something that might be beneficial for you, remembering to follow the appropriate precautions.

In conclusion, Russell reported that in this phase 1 feasibility study, yoga improved posture, chest wall excursion, lower extremity muscle performance, and the self-reported body/image perceptions.  

In my opinion, exercise is an extremely underutilized tool to improve health outcomes for CF patients...and basically everyone else (in the U.S., at least!).  While we don't have a ton of evidence from a large scale study on the benefits of yoga specifically, there is PLENTY of evidence regarding the benefits of regular exercise.  Maybe yoga doesn't sound so great to you...and that is OK!  The best type of exercise will be something you enjoy, so that it will be done consistently.   Since no new breakthrough therapies are hitting the market today...why not try EXERCISE as a natural, effective way to provide multiple health benefits?  I know that when I recently attended a "restorative yoga" class with my friend Savannah, I left the class feeling awesome--both physically and mentally.  I think that the attention paid to breath control in yoga makes it a particularly attractive option for patients with pulmonary dysfunction.  

The next talk I want to summarize deals with a topic that some people wouldn't consider CF related at all, but I will argue that mental health issues can have deep and long lasting effects on health for both CF patients themselves, as well as their family members.  As a CF mom, and a member of the Patient Engagement Advisory Committee for the CF Foundation, I've come to realize that mental health simply cannot be segregated from our physical health.  Babies and young children are absolutely dependent on their parents for everything from proper nutrition to adherence to their prescribed CF treatment regimen.  If a caregiver is struggling, negative effects can ripple throughout the family, and ultimately affect the child.  When I was a new mother struggling with Brady's CF diagnosis, I would have never even considered bringing up my own mental health struggles with Brady's CF clinic team...even though I realize now that I probably should have.  It didn't seem like the time or place for me to air my own concerns about how out of control I felt over my emotions, and life in general.  Parents of children with special needs often put their own problems on the back burner, and find the topic to be too personal and painful to discuss.  I struggled with depression, crippling anxiety in regard to clinic visits, and persistent sleep problems during Brady's infancy.  I didn't want to admit that this time in my beautiful son's life was a really dark and scary period for me. I just figured that because CF sucks so much, I would probably never feel really good again, and that the depression and anxiety were par for the course.  I'm sure that my struggle is not unique, and that many of you may potentially relate to the helpless state I found myself in.  

What Healthcare Providers Need to Know About Postpartum Depression (Associated with Newborn Screening), But Were Afraid to Ask.
Audrey Tluczek

This discussion dealt particularly with postpartum depression associated with a CF diagnosis following newborn screening.  The speaker explained that she uses the term "postpartum depression" simply because it is defined by the onset of depression symptoms coinciding with the birth of a child. Unfortunately, for families with a newly diagnosed infant, that early period can be so overwhelming and scary.  Many would probably consider postpartum depression/anxiety a problem exclusive to mothers--but when management of a chronic disease in a child is required, it can be just as pronounced in FATHERS, GRANDPARENTS, or anyone that is functioning as a care provider for the child.  Tluczek discussed the need for more formal depression screening as a part of the regular clinic visit for families with newly diagnosed infants, and training of the clinic care team to provide useful interventions.

Clinic teams are becoming aware that mental health assessments NEED to become an integrated part of CF care.  Unfortunately, many members of the care team may not be formally trained to recognize the symptoms.

For family members exhibiting signs of depression in association with care of the infant, treatment options can include psychotherapy, support groups, medication, and hospitalization for the most severe cases where the health of the individual or child is believed to be endangered.

This is important, because depression negatively impacts parent/child interaction.

I didn't realize how much my own mental health might be negatively affecting the precious child I wanted so desperately to protect.

Having a good relationship with a stable partner, family support, and the ability to provide for the basic social and economic needs of the family were found to be important factors in lessening the negative effects of post diagnosis depression. 

The CF Foundation recommends that mental health screenings should be a part of the regular clinic experience for both CF patients, and their families.    
In this day and age of comprehensive care, I think it is so important that we feel that we can discuss depression, anxiety, OCD symptoms, or any mental health concerns with the CF care team.  Looking back, I certainly wish I hadn't suffered in silence for so long.  It is equally important that care teams are appropriately trained to recognize the symptoms of mental health issues, and provide options for treatment that may include referral to an outside professional.  This topic is simply too important to remain taboo.  It should be noted that while this talk focused specifically on postpartum depression, mental health concerns can come up at any time, especially with the demands of chronic disease management.  These issues are important to address at any stage of life.

I know many of my readers tune in to the blog for science updates.  I hope I haven't tarnished my rep by devoting this entire entry to the fine art of living and thriving with CF.  Tomorrow, I plan to return to the cutting edge...and honestly, I need a night to sleep on the information I heard this morning in Symposium 8: Gene Editing Strategies for Therapy and Research.  I believe that the future cure for EVERYONE with CF--regardless of their mutation, may become reality through one of techniques discussed in that room.   Until tomorrow...