Tuesday, November 20, 2012

Almost a Cure

I've had to explain what cystic fibrosis is to a lot of friends, family, and strangers over the years.  Since Brady started taking Kalydeco, I've found myself struggling with my spiel (a great problem to have!).  Let's examine the facts:

1) Brady still has cystic fibrosis.  He still has the genetic mutations he was born with (G551D, DF508). 

2) He still takes pancreatic enzymes, special vitamins, and several other prescription meds as a result of being born with CF.  His pancreas has suffered "permanent" damage that Kalydeco hasn't corrected.

3) According to the gold standard diagnostic test for CF--the sweat test, Brady no longer diagnoses positive for cystic fibrosis (last test was 17 mmol/L, 17!!!  Well within the normal range). 

4) Kalydeco has corrected the basic defect of cystic fibrosis in Brady's body (dysfunctional CFTR has now become functional).  Functional CFTR leads to thinner mucus, improved mucociliary clearance, and restoration of proper pH in the lungs and digestive tract in the body (CFers typically have an overly acidic environment in their lungs and digestive tract, promoting infection and impairing digestion.  Kalydeco restores the body's correct pH, giving the body innate bacterial killing power.).

5) In CT scan, Brady's lungs currently show "No visible damage" and appear to be functioning completely normally.

6) Today, Brady has absolutely no lung or sinus symptoms of CF :)

7) Kalydeco is anticipated to add decades and immeasurable quality to Brady's life.

8) If Brady stops taking Kalydeco, the symptoms of cystic fibrosis will return almost immediately.

So what does that all mean?  It means my explanation of Brady's condition just got a lot more complicated...I have caught myself using the following phrase recently because I don't know what else to say:
"It is almost like a cure for him." 
I hesitate to include that word at all--cure--because I am really not sure what that means, and because that word holds so much power.  I know that unless you are a part of the CF world, or perhaps have seen a news piece about Kalydeco, most people won't understand why Kalydeco is such a big deal for us.  They won't understand that it has changed everything we do and think about every minute of the day.  I mean, it isn't a real cure, because Brady still has CF and has to take that magic blue pill twice a day or he is back to old-fashioned CF...BUT, as long as he is taking Kalydeco, his body doesn't realize it has CF.  Almost a cure is good enough for me. 
With all this in mind, my husband, Brady's Dr., and I have some decisions to make about how to move forward with treatment.  Brady is currently still doing once daily Pulmozyme and 15 minutes twice daily on the Vest.  We have been very slow and deliberate in removing treatments from his regimen because his safety is ALWAYS our #1 priority.  We don't want to remove any treatment that could potentially still be beneficial to him. Theoretically, and from everything we have clinically observed in Brady--he shouldn't really need ANY lung treatments or lung clearance anymore.  Not even the experts at the NACFC seemed to have a real answer for us on the best path forward with treatment...the ball is in our court.  
The Scenario:
We are planning a big family trip to Spain over the holidays and I have had a goal in my mind of being able to make that trip without Brady's Vest machine. We have been training Brady on the Acapella device as a more travel friendly option for airway clearance, and would still be able to do manual chest PT in the event that he caught a bad virus and was in need of a good beating ;)  We are taking a portable nebulizer and will be continuing his Pulmozyme treatments as usual.  I am anxious to discuss this again with Brady's Dr. at his next appt. (end of Nov.), and see what he thinks!  Feel free to comment your two cents on the topic!  Take the Vest...or not?
The full-length Plenary Sessions from this year's NACFC are now available online and I encourage everyone to watch!   https://wiww.nacfconference.org/plen.archive.html

Sunday, October 14, 2012

NACFC Update: Exciting new methods of Fighting Pseudomonas infection in Cystic Fibrosis!

CFTR modulator data has taken center stage in my Conference blogs so far, but I'm equally excited to summarize some other really interesting talks about new methods to treat Pseudomonas infection in cystic fibrosis.  As we know, chronic infection in the CF lung leads to loss in lung function and bronchiectasis (irreversible widening and loss of elasticity in the airways) over time.  Even if you have an effective antibiotic to treat Pseudomonas, very little medicine is able to penetrate the “biofilm” inside CF lungs to reach the infecting bug.  Think of the  biofilm as an impenetrable layer of super-slime.   When a pathogen enters the CF lung, it finds a nice cozy home in the already thick, sticky CF mucus.  Tissues become inflamed and as cells die, long strands of DNA are left behind, that further bind mucus together.  This makes the environment even more hospitable for bacteria and so the vicious cycle of inflammation, infection, and impaired mucociliary clearance in the CF lungs has begun.   Chronically infected areas of the lungs begin to form these “biofilms” that can eventually cover the entire inside surface of the airways.  Searching for new ways to penetrate the biofilm have yielded some exciting new lines of potential treatments for CF infections.

Before I get into this new research, I want to tell a short story about a job I had in college and I promise it will all make sense in a minute.  One summer I worked with an Entomologist (scientist who studies insects) at WSU.  We worked with local organic farmers to help them eliminate problematic bugs from their crops without using pesticides.  For example, if a farmer had a problem with a particular beetle eating their potato crop, they would hire us.  Our solution was to introduce a different insect to their fields, which didn’t eat potatoes, but absolutely loved eating those problematic beetles.  After the beetles were eaten up, the introduced insects would move on, because their food source would be depleted.  By contrast, if a pesticide had been used to deal with the problem, ALL the bugs in the field would have been killed, even the beneficial ones.  Plus, there would have been a bunch of chemical toxins introduced to the soil and crops.  This natural method of pest control made a lot of sense to me.  Now back to Pseudomonas…

Abstract 270: Rational Design of a Pseudomonas Aeruginosa Bacteriophage Therapeutic and its Efficacy in a Murine Lung Infection Model.   Presented by David Harper Ph.D
Just as there are countless viruses that can specifically infect humans, there are also millions of viruses in our environment that only infect bacteria—bacteriophages.  Bacteriophages are already present in our bodies by the trillions and are completely harmless to us.  They can only survive if they are able to infect a “host bacteria.”  Bacteriophages kill their host immediately upon infection.  Bacteriophages are also host specific, which means there are certain varieties that only infect Pseudomonas aeruginosa (Pa).  I certainly like the idea of tiny Pseudomonas assassins (trigger 007 theme music)!  This line of research explores whether using a bacteriophage cocktail specific for Pa might be an effective way to treat chronic Pa infection in the CF lung.  The investigator used 3 Pa specific bacteriophages in his “killing cocktail” and administered the treatment to mice infected with Pa.  What he found was really amazing.  Unlike antibiotics, bacteriophages easily penetrated the biofilm.  They proceeded to infect and kill the Pseudomonas, and even disrupted and disseminated biofilms.  Because bacteriophages have no interest in infecting anything besides their specific target, there was no collateral damage to the airway tissues.   In the mice, it was shown to be an extremely effective at killing Pseudomonas previously THRIVING in the biofilm.  For a bacteriophage, visiting a biofilm is sort of like going to an “all you can eat buffet.”  They love it!  There are bacteriophages specific to both mucoid and non-mucoid strains of Pseudomonas, so I guess what I’m saying is—You’d better keep both eyes open Pseudo…there might be a new bug getting introduced into the potato field!  I think the guy who came up with this idea is a freaking genius and I sincerely hope we can see something like this translate to human infections in the near future.  There are plenty of negative issues surrounding chronic antibiotic use, including: bacterial resistance, unpleasant side effects, ineffectiveness because of inability to penetrate biofilm, and more indiscriminate killing of bacteria (they kill the good guys along with the bad guys).  This bacteriophage treatment technique could bring something totally new to our tool kit for treating CF, and might even help solve one of the biggest issues facing the world of medicine right now—antibiotic resistance.  I haven't been able to stop thinking about this research since I watched the presentation...or my summer killing problematic bugs in potato fields! 
Studies are planned in humans, but no timeline was given yet.  This research was performed by Blake, K.L; Henry, M.; Debarbieux, L.; McConville, M.L.; Prosser, I.M.; Parracho, H.M.; Enright, M.C.; Harper, D.R.  AmpliPhi Biosciences, Bedford, UK and Institut Pasteur, Paris, France. 

A second exciting presentation regarding the fight against Pseudomonas infection was:

Abstract 268: ALX-109 Potentiates the Effect of Tobramycin at Killing Pseudomonas Aeruginosa Biofilms on Human Airway Cells.  Presented by Sophie Moreau-Marquis, Ph.D. 

For reasons unknown to researchers, the iron concentration in the CF lung has been found to be 400x higher than in the non-CF lung.  Iron has been shown to promote the growth of Pseudomonas biofilms on airway cells.  This research looked at the possibility of chelating excess iron in the lungs to allow antibiotics to more effectively battle Pa infection.  Chelation is a process where one chemical combines with another, to render a new stable model that is not reactive (it sequesters, or holds the iron captive so it can’t react with other molecules).  ALX-109 or Alaxia, is an iron-binding glycoprotein, that has recently been granted “orphan drug” status by both the FDA and EMA. 

In the study, ALX-109 was combined with Tobramycin and tested on Pa strains isolated from the sputum of CF patients. The Tobi + ALX-109 combination significantly disrupted biofilms.

It was concluded that an inhalation therapy combining Tobramycin with ALX-109 may be beneficial to CF patients infected with mucoid clinical isolates of Pseudomonas.  This research was conducted by Moreau-Marquis, S.; Stanton, B.A. Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH.  Phase 1 clinical trials are planned.

I love the idea of getting some new powerful weapons to fight CF infections and I encourage anyone interested in participating in clinical trials to sign up for email alerts from the CFF here! http://www.cff.org/research/ClinicalResearch/Find/ClinicalTrialAlerts/

We finally made it home from Orlando this afternoon.  What a long trip from Orlando to Northern Idaho!

Saturday, October 13, 2012

NACFC Update--Caring For Patients on Kalydeco: Emerging Topics in CF Management.

Brock and I started off today's session by filming an interview for the CF Foundation about the positive impact of Kalydeco on Brady and our entire family.  We also filmed "My Dream for CF" videos.  After that we headed to the third and final Plenary Session of this event entitled: Adherence...Where's the App for That?  I will go into the details of this session later, but will say this--new therapies and medicines are of absolutely zero use if they do not get utilized by the patient.  As a parent of a young CFer, I understand that there are challenges in maintaining the rigorous CF treatment schedule.   This session focused on ways to help patients overcome those barriers to become more compliant with their treatments, which ultimately leads to better health outcomes and fewer hospitalizations.  There are all sorts of cool new apps and web based technologies coming along to make staying adherent EASIER on the patient.  The future of tracking your PFTs may become as easy as simply blowing into your smartphone, which will then automatically send the data to your care center's database.  How awesome is that? 

We attended talks all morning, which I will also summarize at some point, but right now I want to focus on the most interesting information I got today, which came from a "Luncheon Roundtable" session.  There are dozens of highly specialized topics to choose from in these sessions, which are discussed in an informal manner by the 10 or so attendees that fit around your table.  There was no question which discussion I wanted to be a part of--Caring For Patients on Kalydeco: Emerging Topics in CF Management.  Each table has a "moderator" or expert who leads the discussion.  Our moderator was Dr. Frank Accurso M.D. University of Colorado, Denver.  We didn't have a ticket to attend this talk, but eventually got seated and entered the discussion already in progress.  We had a nice variety of guests at our table, consisting of nurses, a Pulmonologist, a GI doc, and a pharmacist.  When we were finally seated, we were asked to introduce ourselves and describe why we were there and what we hoped to learn.  When I announced that we were parents of a 5 year old that had been on Kalydeco for over 8 months who showed a drop from 105 mmol/L to 17 mmol/L on Kalydeco and a CT scan showing "no visible damage," and our goal was to learn how to proceed with his care...well, we suddenly became the focus of interest for everyone else at the table.  I'm not sure what they were discussing before we arrived because as soon as WE got there, we were bombarded with questions.  First of all, every one of them was surprised that Brady had Kalydeco and wanted to know first and foremost how we had obtained it.  I described that we had been discussing Kalydeco with Brady's Pulmonologist since infancy and had prepared a strong case for his medical necessity of the drug.  We didn't do anything special, or secret...we simply obtained a prescription from Brady's Dr., submitted it to CF Services Pharmacy, submitted the required "prior authorization form," and provided a load of Brady's medical information at the request of our insurance company.   It was approved and shipped to our house just like any other medication that Brady takes (except you have to sign for this super expensive one!).

On a side note, I think there is a big misconception out there that no one can get Kalydeco unless they are G551D and over 6 years old.  That simply is not true.  The only thing you need to obtain Kalydeco is a prescription and a way to pay for it (either by being INCREDIBLY independently wealthy or having insurance coverage).  Of course, getting insurance coverage for "off-label" cases has proven to be the tricky part, but many patients/parents don't even try because they have been told that it is "impossible."  Everyone told us that also, but I hope our experience illustrates that the "impossible to get" concept is BULLSHIT.  Vertex pharmaceuticals has ABSOLUTELY NOTHING to do with who is able to take Kalydeco.  They can't provide any financial assistance to patients attempting an off-label Rx, because they don't want to get sued, but drug makers do not provide medicines to patients directly (except on compassionate grounds in the case of Kalydeco), pharmacies do.  I mean, do you think that every time a new prescription is submitted, that the pharmacy calls Vertex to ask if it is OK??  Hell no.  That is not how it works.  All the pharmacy cares about is how you are going to pay for it.  If you have insurance coverage, you are golden.

After describing all the incredible changes we've seen in Brady, everyone turned their focus back to the topic of--How do you move forward with treating CF patients on Kalydeco?  Should the regular schedule of medicines and therapies be maintained, or is it OK to drop some?  Are there some patients that may eventually be able to stop ALL of their regular CF therapies?  I wish I could say that there were clear answers to these questions, but the consensus at the table was that NO ONE KNOWS!  Everyone agreed that the treatment of these new Kalydeco patients must be addressed on a case-by-case basis, with the most important factor being how much permanent lung damage/scar tissue/bronchiectasis each patient had obtained before the initiation of Kalydeco treatment.  The idea is that the Kalydeco has the ability to halt further progression of the disease in certain patients (like those with G551D or other gating mutations).  If a patient starts Kalydeco BEFORE much damage has occurred, there is an opportunity to drop some of the regular CF therapies.  On the other hand, patients in the end stage of disease with considerable scar tissue may need to remain on all of their maintenance meds in addition to Kalydeco.  Think of it like this--if someone smokes for 30 years and then stops, they will certainly experience an improvement in their lung function, but the lungs have suffered some permanent damage and will never reach the same level of function as someone who has never smoked in their life.  It is a similar situation with CFers on Kalydeco.  With that  being said, the discussion then moved back to Brady's case and the question then turned to, Which medication to you remove first and why?  Is it more important to stay on Hypertonic Saline or Pulmozyme?  What about airway clearance?    We described our rationale for choosing to slowly wean Brady off of Hypertonic Saline first (which Brady began at 20 months old, and used to do twice a day).   Hypertonic Saline is designed to temporarily rehydrate the airway surface liquid (ASL) on the lining of the lungs, allowing for better clearance of particles and pathogens.  Kalydeco has also been shown to rehydrate the ASL, but through the mechanism of restoring proper chloride transport out of epithelial cells by activating CFTR function.  We decided that because Pulmozyme works by a different mechanism of action (cuts up long strands of DNA left behind when cells die in the lung.  Those strands can contribute to the formation of biofilms by binding mucus together).   Some people at the table agreed with us, others thought that Pulmozyme should be the first of those two meds to go because of its high cost.

We also discussed whether patients might be able to clear infections from their lungs and no longer require antibiotic therapy.  Most agreed that they would need to see more convincing evidence than a "clean" throat or sputum culture to be really sure that the infection had been cleared (there is lots of evidence that throat cultures do NOT give an accurate picture of what is growing in the lung).  Bugs residing deep in the lower airways are often not reflected in throat or sputum culture, but can be picked up by techniques like broncheoalveolar lavage (BAL).  BAL is an invasive technique where a liquid is squirted inside the lung and then collected and cultured.  You can imagine that BAL is more difficult to perform, but yields a much deeper understanding of the bacterial environment inside the lung, than swabbing the back of the throat.  Again, no one knew any single correct path forward.

This year, new data was presented that Kalydeco changes the pH in both the GI tract and the airways, restoring the body's natural ability to kill bacteria and pathogens.  CF patients typically have a more acidic environment in their airways and gut because of the body's impaired ability to secrete biocarbonate (a base that neutralizes acid).  The more acidic the environment, the less natural "killing power" your body has.  Patients taking Kalydeco were able to restore normal pH in their airways and gut, which leads us to believe that complete eradication of infection is at least possible

At this point, Dr. Accurso announced that he had to leave for a different meeting, and he brought in a new moderator for our discussion.  I desperately asked him to answer some questions about the "trials of 1" initiating in Denver, before he left, but his response was that I could email him with those questions...which I will certainly do.  I'm so sorry I can't provide more details about this. I promise I will try to get those answers!  Again, I wish I could write more this evening, but I only have a few minutes left to get ready for the "CF Prom" tonight!  One last important little tidbit that I forgot to mention earlier is that I asked Dr. Accurso why we saw Brady's sweat chloride first drop from 105 mmol/L down to 48 mmol/L, and then saw a further decrease down to 17 mmol/L.  He asked me if Brady had eaten pizza or some other super salty food before his 48mmol/L result.  I questioned why that would matter and he revealed to me that salt intake can affect sweat chloride results.  The take home point is super excessive sodium intake can artificially increase the sweat chloride score and should be avoided just prior to the test (like the day before).  I'm not suggesting that you eliminate salt intake--rather, adjust to more "normal" dietary sodium rather than the stardard high salt intake typically recommended for CFers to get a true measurement.  That was news to me!

Our flight leaves tomorrow morning at 7:30 a.m.!  I miss Brady so bad!! 

Friday, October 12, 2012

Plenary 1

It will probably take me several months of blog entries to detail everything I want to say about this year's NACFC, but I have to start somewhere.  This entry will summarize what was discussed in yesterday's Plenary Session.

Plenary Session 1: Reversing the Basic Defect: A Vision for the Future
Speakers Steven M. Rowe, M.D., MSPH and William Skatch, M.D.

In my mind, the overarching theme of this talk was: OK, we've fixed G551D, we think that Kalydeco will be expanded to all Class 3 and 4 mutations, and some others with residual CFTR.  Here is how we are going to go about figuring out a similar treatment for every last CF patient.

First, Dr. Rowe presented some really interesting information from the GOAL study, which is an extended study on Kalydeco in patients to examine secondary endpoints not included in the previous trials.  They are interested in understanding some of the unexpected/unexplained effects that have been seen in patients on this therapy.   Exactly how has CFTR modulation affected the patient's mucociliary clearance (the ability of those little hair-like projections inside the lung to sweep particles and bacteria out)?  How does Kalydeco affect intestinal and/or lung pH and sweat rate?  His focus was on the mucociliary clearance (MCC) endpoint.

He showed how the typical CF lung has severely impaired MCC because those little hairs are bogged down by thick mucus and basically just stop moving all together. This is part of the vicious cycle of infection and inflammation that takes place in the CF lung.  When the cilia stop moving, the body's natural ability to rid the lung of harmful pathogens becomes severely impaired.  They were able to show that CFTR modulation with a drug like Kalydeco could restore mucociliary clearance and movement of cilia in patients.  Boom.  This is the first ever data to show a marked improvement in MCC in CF patients. 

He also announced that the Kalydeco trial for 2-5 yr. olds "officially" had been cleared to begin enrolling patients as of yesterday (10/11).  If you are interested in this trial and you haven't already spoken to your CF care center, do it now.

He also discussed how Kalydeco might be effectively used in other CF populations and how they plan on moving forward with testing this concept.  They are using two approaches: 1) The Genotypical Approach and 2) The Clinical Approach.  This means that they are using genotype information (which mutations the patient has) to identify some candidates (for example, the upcoming trial for R117h, which is a class 4 Conductance Mutation).  Other candidates might be found because they clinically present with symptoms suggesting some residual surface CFTR function--such as those who are pancreatic sufficient or have lower sweat chloride scores (in the 80 mmol/L) range.  He went on to describe the small study that will be taking place in Denver which is the new "trial of 1" design format.  In this format, there is no placebo and the efficacy of the treatment is based on the patient's response.  I am hopeful that this type of study design will open up a lot of doors for future trials in rare mutations, who might otherwise be excluded from large scale studies.  This is good news for heterozygotes because it is so incredibly difficult to predict how those patients will react, and right now they are being excluded from taking part in CFTR modulator studies.  We've got to change that!

Class 1 Mutations:
Next, he summarized the results of the Ataluren trial.  I wrote about this briefly yesterday.  Basically, Ataluren didn't produce statistically significant study enpoints, and also exhibited an antibiotic interaction with Tobi and other aminoglycosides--which completely nullified any treatment effect.  He mentioned a new compound called NB124 that seems like a promising candidate for promoting translational read-through of the protein to produce a full length functional CFTR.  He also discussed combining this compound with a potentiator to enhance its effect.  Getting NB124 to market is going to take some time.

Class 2--F508 and others
They are super focused on addressing the F508 mutation since 50% of the CF pop. is homozygous and 40% of the CF pop. has at least 1 copy.  F508 exhibits several defects in the cell which cause its ultimate dysfunction: 1) Improper protein folding and assembly, 2) Gating defect if any CFTR does manage to reach the surface, and 3) Instability at the cell surface (increased cell death/turnover).  I wrote a detailed blog about this after last year's NACFC, and this year they understand in even greater detail the various issues with F508.  Multiple corrections must be made for this protein to successfully form, move to the cell surface, and then WORK once it gets there.  The VX-770, VX-809 combo is able to rescue approximately 30% CFTR function, enough to produce meaningful clinical changes in patients.

Class 5 and 6 mutations
I didn't catch any concrete details on how to address these two classes, which are not as well understood as some of the others.  He concluded that "further studies" will be needed for all heterozygotes, which encompasses ALMOST everyone in these two groups.

Lastly, Dr. Rowe was excited to announce how many new companies had started CFTR modulator programs like: Pfizer, Genzyme, and N30.  Vertex DEFINITELY needs some competition! Now it is a race to the finish line!

Dr. Bill Skatch spoke next.  He is a member of the "CFTR Folding Consortia" as well as the "CFTR Structure Consortia."  In other words, he walks, talks, and dreams CFTR!!  His talk was very technical, but featured some of the coolest graphics I've ever seen to describe the steps needed to produce functional CFTR in the body.  His talk went much deeper into the details of F508 dysfunction.  He explained that CFTR is like a "molecular jigsaw puzzle."  There are twisted pieces, globular pieces, and straight pieces.  They must all be the correct shape and come together in a step-by-step fashion.  It is such a complex process that it takes the human body 7-8 minutes to make a single CFTR molecule!  There are other proteins called "chaperones" that help regulate folding and speed.  They are learning that these chaperones are an important part of this process.  He described that the final protein must exhibit exactly the right amount of stability, and flexibility at the cell surface to keep from "unraveling" and degrading to become useless in Chloride transport.  He described in great technical detail how they can test this stability by measuring how much energy (in the form of heat) it takes to cause the protein to unravel and degrade.  They need to make CFTR stable enough to remain functional and intact at human body temperature (F508 mutants are unstable at body temp).  He explained the "ceiling" affect that single corrector combinations inevitably hit because one corrector can't take each of these aforementioned problems into account.  Then he described how combining several correctors to account for the multiple dysfunctions was the path to restoring 70-80% functional CFTR for F508.  They know what they are doing. I am headed out the door to a dinner reception!  I may post more later depending on how much wine I drink...Please excuse any errors or typos.  I am trying to be fast!

Thursday, October 11, 2012


It is hard to believe that so much activity and information can possibly be packed into a single day...This morning Brock and I kicked off the NACFC with a breakfast meeting with Dr. Beall.  I get incredibly nervous when I know I will be meeting with Bob, but after that first hug and bout of tears, it only takes minutes before his demeanor puts me at ease.  We took the opportunity to share all the details of our Kalydeco experience with him and gave him the book we made filled with the "true Kalydeco stories" from other patients.  Hearing those success stories is extremely rewarding for Bob and if you contributed to the book, Thank you.  He truly loved it.  I feel like a big hog, because all the "thanks" has been given to me, even though all I did was assemble the stories.  When I get back home, I will post some pics of the final product.  It was such a privilege to put together so many beautiful stories. 

* The most exciting and fantastic news that I have to report from today is the positive buzz regarding the VX-809/VX-770 combo!   Tweaking dosages of both compounds has enabled them to reach the statistically significant improvements they were looking for.  They were able to rescue approximately 30% CFTR function, which is sort of the magic number to see big clinical improvements ((Kalydeco rescues approximately 50%, for perspective).  HELL YA!!  I'm super encouraged that this combination will be progressing to phase 3 trials, and could be coming along sooner rather than later.  Even if it isn't the "magic bullet" that Kalydeco is for gating mutations, this combo could go a long way toward improving/stabilizing lung function and increasing quality of life. Isn't that what it is all about? 

* The recently listed trial on clinicaltrials.gov taking place in Denver for heterozygotes IS the individualized "trial of 1" or "trial in a box" design that Peter Mueller of Vertex proposed earlier this year!  http://iom.edu/~/media/Files/Activity%20Files/Research/GenomicBasedResearch/2012-MAR-21/3%20-%20Peter%20Mueller.pdf  It is a small initial trial, but this is really exciting news for heterozygotes, patients with rare CF mutations, or anyone who wants to see individualized genetic modifier treatments reach patients FASTER.  This will enable patients with any suspected surface CFTR activity to trial Kalydeco and decide whether the therapy should be continued based on their own body's response.  Again, HELL YA!!  

* The overall feel I got today regarding Ataluren, is that this drug hasn't lived up to expectations.  There was some discussion about the possibility of combining a drug to increase translational read-through of the CFTR protein (like Ataluren), with a potentiator like Kalydeco to boost results... But, it was mentioned several times that they already have discovered compounds that work BETTER than Ataluren ever did at improving protein read-through.  The biggest problem with Ataluren is that it binds to the same site on the cell's ribosome as some inhaled antibiotics like Tobi and other aminoglycosides.  Basically, Tobi and Ataluren need to work on exactly the same spot in the cell...if Tobi is there, Ataluren can't bind and do its job.  Inhaling Tobi almost completely nullifies the therapeutic effect. Damn.  The Ataluren presentation was very vague and I still don't have any answers about what their steps are moving forward (I even mustered the balls to stand up to the mic and ask the presenter a question about their plans for further trials or to combine with another compound and wasn't given a conclusive answer.).   Again, I'm not certain about the future of Ataluren, but my overall feeling is pretty negative about this drug reaching the market to treat Class 1 mutations on its own.  The primary trial endpoints were not met, and the antibiotic interaction problem may be too large to overcome.  Again, the information given was quite vague, and I just want to reiterate that this blog is my interpretation of what was presented.  It was never directly stated that Ataluren won't move forward.  In their words, "we are working with regulatory bodies in the U.S. and Europe to determine the best path forward."  What does THAT mean?? 

* Lastly, I want to mention that the first Plenary session today was amazing.  There was a SHORT celebration of the success of Kalydeco, followed by details of their plans to move forward to treat the rest of the CF pop.  They are impatient and understand the urgency to keep progressing.  They now understand, in dizzying detail, the dysfunction of F508 and have a road map for correcting it.  As mentioned earlier, there is positive buzz about the VX-809/VX-770 combo, but the "second generation" of combos already being tested in the lab have the potential to rescue 70-80% CFTR function--far exceeding the effect of Kalydeco for gating mutations.  To achieve these results, the second generation drugs must address the multiple dysfunctions that this mutation presents: 1) folding, 2) stabilization, and 3) gating.  I said it last year and I'll say it again: THEY HAVE IT FIGURED OUT.  IT IS A MATTER OF TIME AND MONEY.  I'm more optimistic than ever after a full day of lecture.  I have so much more to say, but it is after midnight and I have another full day tomorrow.  I plan to write summaries of the individual talks I attended today, which focused mainly on F508 correction and early CF lung disease.  Brock and I also attended a fancy dinner this evening, where my Kalydeco tattoo was finally uncovered to be appreciated and photographed by many : )  The speakers at this dinner gave moving presentations that didn't leave a dry eye in the house.  I am experiencing emotional overload.  I may have finally exhausted myself to the point of sleep.

Sunday, September 30, 2012

Brain Pain

I will never ever forget the fear that comes along with dealing with CF, but it has been over 7 months since Brady has been on Kalydeco now and I can feel myself adapting to a new normal.  The fear is losing its grip and I've even found myself away from home WITHOUT hand sanitizer a time or two (gasp!).  Before February 10th, when Brady took his first dose, I simply could not conceptualize what my post-Kalydeco world would look or feel like.  Getting him that medicine was my singular focus and goal.  Well, he got his medicine and time has marched on.  Since I'm one of those people that like to have control of everything, this "after" time has been really refreshing for me.  For once in my life, I feel like instead of making lists and plans...I am just enjoying the ride.  There have been a few surprises for me along the way--some fantastic, others not so great. 

#1--I thought that once Brady got Kalydeco, everything would be great and I could stop worrying about CYSTIC FIBROSIS.  The reality is that I am tortured by the fact that others who could benefit from Kalydeco can't get it because of the many roadblocks to access.  This feeling mixes with the guilt of being one of the first families to benefit and rips my heart to shreds.  Overall, I feel extremely disillusioned with the world because people that I care about will get sicker or need a transplant because they don't have the $300K/year to pay for this drug. Or maybe their Dr. just isn't on board with writing the Rx because he isn't educated enough about the potential.  It hurts my heart and my brain.  This feeling is only amplified as I see how wonderful Kalydeco is working for Brady. 

#2--I thought that once Brady got Kalydeco, I could stop worrying about him all the time and everything would be just peachy.  What I've found instead, is that every parent worries about their children all the time no matter what.  Now my worry has shifted to what some might consider more "normal" parent concerns.  I spend a lot more time worried about Brady getting kidnapped (and hoping the kidnapper will at least remember to take the Kalydeco!), or hit by a car when he is playing outside.  I worry about him picking the wrong person to date or experimenting with drugs...With CF on the sidelines, my mind has been more free to just wander.  The realization I've come to is that there is ALWAYS going to be something to worry about.  I can't control the world (as much as I want to!).  All I can do is love my family and friends every day and cherish the health and happiness that we have in this moment. 
Enjoying our fall Farmer's Market!

#3--I have found tremendous JOB SATISFACTION.  Let me just reiterate that I am unemployed (convenient, huh?).  I don't work for the CF Foundation.  I don't work for Vertex.  I wondered what the hell I would do after Brady got Kalydeco and I didn't have to dedicate every second of my life to fighting for this medicine.  I'm so lucky that my husband has an excellent job that has allowed me to stay home with Brady from birth to present.  I've been able to teach Brady so many things in our time together and I've found myself a job as a caretaker/cheerleader/mentor/translator/fundraiser for the CF community.  I remember the first few months after Brady's diagnosis as the darkest time of my life.  Sharing research information with families makes me so happy because scientists are on the right track and there is GOOD NEWS.  It is incredibly empowering and wonderful.  I don't have any conflicts of interest.  My only concern is helping CF patients and families get what they need.

#4--I thought that once Brady got Kalydeco, life would be calm and serene.  Man I am an idiot.  I've been so "worked up" since Brady started taking the drug that my insomnia is worse than ever!  Since I've been subsiding largely on coffee and champagne for the last several weeks, I'm sure I'm working on an ulcer flare-up also.  Watching Brady's transformation has been so thrilling.  Every new test result sends me right back over the moon (like his most recent sweat test: 17mmol/L!!  I walked around yelling 17?!?! for days).  My heart is all wrapped up in all these other CF families and I constantly have YOU/YOUR child's mutations swimming around in my mind.  I'm working on my little notebook to take to the NACFC with all the questions I want to ask, and all the specific mutations I want more information on.  Basically, I've worked myself into a frenzy.  And because I attended the Conference last year, I know exactly how awesome it is going to be! The thought of sitting down to dinner with "CF Celebrities" makes my palms sweat!   Not to mention that I have a huge knot in my stomach wondering what new data will be presented because I know how much it means to CF patients and families.  I know how much is riding on the results of that research.  Will an effective combo be ready to market in 2016?  Or will it take longer? 

Is "Brain Pain" a real condition??

I got a haircut today, bought new luggage,  and am trying to figure out what I'm going to wear?!  It's crunch time!  I seriously hope I don't just drop dead of a heart attack from all the excitement!

Wednesday, September 19, 2012


Last year I attended the NACFC in Anaheim and blogged about my experiences there.  I've been reviewing what I learned and working on my plan of attack to get the answers I'm looking for this year.  Here is my first NACFC 2011 post if anyone else is interested in reviewing: http://luckycfmom.blogspot.com/2011/11/prelude-to-kiss.html 

As I prepare to attend the NACFC next month in Orlando, I'm thinking mostly about:

1) Combo Trials--I will be looking for details on how both VX/770-VX/809 and VX/770-VX661 are progressing.  I am also interested in seeing if they will be presenting a new 3 drug combination to start down the development pipeline.  Last year, it was revolutionary news that they had discovered 2 misfolding problems that needed correction for DF508.  In the lab, 3 drug combinations (2 correctors to treat each misfolding site + Kalydeco to open the CFTR channel once it reached the surface) worked REALLY WELL.  A combination like this would be a few years behind the combos currently in trials, but has the potential to achieve the magnitude of change for DF508 that Kalydeco has shown for gating and conductance mutations.  http://luckycfmom.blogspot.com/2012/02/genetic-origami.html

Also within the realm of combo trials, I am very curious how they plan to proceed in trials with heterozygotes.  Is there new "transcomplementation" data being presented this year?  http://luckycfmom.blogspot.com/2012/03/calling-all-heterozygotes.html  What about the "trial of 1" concept proposed earlier this year by Peter Mueller of Vertex?  http://iom.edu/~/media/Files/Activity%20Files/Research/GenomicBasedResearch/2012-MAR-21/3%20-%20Peter%20Mueller.pdf
Is this recently announced clinical trial a "trial in a box" as described by Mueller?  http://clinicaltrials.gov/ct2/show/NCT01685801?term=vx-770&rank=19

2) Kalydeco questions like: Will they be moving forward to see Kalydeco marketed to COPD patients? http://www.sciguru.com/newsitem/14332/cystic-fibrosis-drug-kalydeco-may-be-useful-treating-copd-smokers   If they open up the market to a large population like this, it could certainly affect the price of Kalydeco.  

What the hell is going on in Europe and other parts of the world in terms of access...or rather, lack of access?!?!  Everyone who read my last blog entry knows exactly how I feel about making Kalydeco available to those who need it. 

I want to take the opportunity to discuss the many off-label prescriptions (because of both age and mutation) have successfully been filled and are showing positive results.  Last year, everyone swore that we would be unable to get Kalydeco to Brady at age 4 1/2 and they were WRONG about that!  Being at the NACFC is going to enable me to sit down to coffee with Bob and give him the real scoop on what is really happening in our CF world.   Last year he called me his, "link" to patients and parents.  I honestly think that the CF community is more empowered and educated than ever before because we've come together to share like a family (and we have the internet!). We are able to learn about the latest research from the comfort of our own homes. I love to hear how many parents are educating their child's DOCTOR about the latest in CF research and newest information on their child's particular genetic code.  We have DEMANDED that our voices are heard, even when our own CF specialists might be hesitant.  I would love to hear more detail on the timeline they see to opening up the FDA approved label to include other mutations and/or children under 6. 

I have lots of other crazy question like: Could a pregnant woman take Kalydeco?  Could meconium ileus, pancreatic insufficiency, and other complications be prevented if the mother of a fetus with G551D(or other mutation positively affected by Kalydeco) began taking the drug during pregnancy and then the infant began therapy at birth?  Can you imagine??  What about how Kalydeco affects other organs besides the lungs?  I've seen Brady's serious sinus issues disappear and that was not a reported or tested clinical trial parameter. Theoretically, Kalydeco should be able to prevent deterioration of other organs such as the liver and pancreas.  Are clinics seeing this in practice?

I realize that there are no real answers to some of these questions, but I'm still pretty curious to sit down with some of these researchers and CFF execs and hash out the possibilities

3) Ataluren
Please.  What is the hold up with information regarding Ataluren??   Are they still planning on marketing Ataluren? I'd like to hear more detail about the side effects they recorded in the clinical trials.  I'm also very curious to hear if they have tested an Ataluren + Kalydeco combination.  This was a concept mentioned as a possiblity at last year's Conference.  If non-toxic in combination, Kalydeco might be able to provide those important sweat chloride changes that they didn't see with Ataluren alone.

These CFTR modifiers are game-changers, and I hope I can report some amazing, awesome news this year!  My husband Brock is attending the Conference with me this time, and we are a great team!  We plan to split up during some sessions so we don't miss any important talks taking place during the same time slot.  He is so excited to shake hands with Dr. Beall and the Vertex team.  Last year, I was afraid that my heart might explode with gratitude as I sat side by side with these brilliant researchers...and that was BEFORE BRADY EVEN GOT KALYDECO!  This year, the "thank you's" will mean even more!!  Stay tuned...these blog updates are about to get really GOOD!  Only 21 more days til Conference!  If YOU have a burning question about CFTR modifiers that I didn't mention, leave me a comment and I'll add it to the list! 

Sunday, September 9, 2012

Case Study

Our friends in Europe are still fighting to get Kalydeco.  Patient advocacy groups have been rallying to pressure governments to move forward with marketing of the drug, but cost negotiations continue to stall distribution.  We  were asked to participate in a "case study" for our European friends to present to deciding bodies about the effects of Kalydeco.  This is what I said,

"Brady Schroeder was born on July 26th, 2007.  He tested positive on a newborn screen for CF and we proceeded with genetic testing, which confirmed his diagnosis of cystic fibrosis (G551D, DF508).  Like most children with CF, Brady has required digestive enzymes and special vitamins to maintain proper growth.  He began having serious upper respiratory issues with sinus polyps at age 3.  By age 4, his sinuses were completely obstructed with CF related nasal polyps, and he had completely lost his sense of smell.  CT scan revealed that the polyps had grown so large, that they had begun to thin and shift bones in Brady’s face.   Bursts of oral Prednisone were used every 8-10 weeks to slow the polyp growth as well as 3X daily steroid rinses for the sinuses.  Even with regular steroid and antibiotic use, the polyps required surgery when our son was just 4 years old.  While this was not a life-threatening issue, it was a huge quality-of-life issue. 
Surgery 1 of 2: Summer 2011

Even though Brady had maintained relatively good lung health for a child with CF, he still did hours of daily nebulizer and airway clearance treatments to slow the progression of CF lung disease.  Prior to beginning Kalydeco, he did twice daily Albuterol/Hypertonic Saline treatments as well as once daily Pulmozyme.  He also spent 20 minutes on his Vest machine twice daily as maintenance.  The regimen of staying healthy with CF is extremely time consuming and exhausting.  It feels like fighting a battle you know you will never win.  Every clinic visit seems to bring a new complication, a new infection, and a new medicine.  It becomes very hard to look toward the future when you aren’t even sure how to get through the current day.  When CF is in your family, the focus becomes keeping that person breathing, growing, and alive.  Friendships and vacations tend to fall by the wayside because an exacerbation or virus too frequently forces a change in plans.  It is impossible to describe the pain and mental anguish of watching your child struggle to breathe within the grips of this cowardly disease. 

On February 10, 2012 Brady took his first dose of Kalydeco.  The first few days after beginning the drug, we noticed a remarkable increase in his energy level and exercise tolerance.  Within 3 days, Brady began breathing through his nose for the first time in over a year.  He stopped snoring and breathing through his mouth at mealtime.  Within a week he began to make non-stop comments about smells in his environment.  Brady hasn’t needed a single dose of Prednisone or antibiotics since beginning Kalydeco, and has also completely stopped the steroid rinses for his sinuses!  It has been a truly phenomenal turn-around that shocked his Ear/Nose/Throat specialist.  Before Kalydeco, we were seeing the ENT on a monthly basis.  Post Kalydeco, we have only seen him once (to document the positive effects of Kalydeco!). 

Brady’s appetite increased noticeably and his growth has been absolutely phenomenal since starting Kalydeco.  He has grown 3 inches in just 6 months on the drug and has gained over 3 lbs, putting him into the 90th percentile for both height and weight-for-age!  He has a decreased need for digestive enzymes, and has fewer stomach aches and CF digestive issues in general. 

Camping trip, summer 2012.  Best summer of our lives!
Brady had a dramatic drop in sweat chloride with Kalydeco.  When he began on Feb. 10, 2012 his sweat chloride was measured at 105 mmol/L.  After 20 days on the drug, we retested and the number had dropped to 48 mmol/L.   After more than 6 months on Kalydeco, we repeated the sweat test and were amazed to hear that it had dropped to 17 mmol/L—completely within normal range, indicating properly functioning CFTR.  The implications of getting a genetic modifying drug like Kalydeco to our son at the early stages of disease are immense.  Because cystic fibrosis is a degenerative, passage of time generally equates to permanent organ damage as a result of dysfunctional CFTR.  Because Brady had suffered little to no permanent lung damage before beginning Kalydeco (as seen in CT scan), he has been able to greatly reduce the number of maintenance treatments he does on a daily basis.  We have completely stopped the twice daily Hypertonic Saline treatments.   We are currently tapering down from Pulmozyme treatments and spending reduced time in the Vest also.  We will continue to be cautious and slowly reduce his treatments under the advisement of his CF specialist, but we can clearly see the day in the near future that our son will no longer need any nebulizer treatments or airway clearance treatments on a daily basis.  Kalydeco has given our young son a second chance at long, healthy, “normal” life.  He will likely NEVER be hospitalized again as a result of CF.  He will not need a lifetime of intravenous and inhaled antibiotics and steroids. I will not have to watch him struggle to breathe.  There is simply no way to accurately describe the enormous positive impact Kalydeco has had on Brady and our entire family!  Watching a disease like cystic fibrosis destroy your child is any parent’s worst nightmare.  You desperately wish there was something you could do to help.  You would give anything in the world to ease their suffering—Kalydeco is that miracle.  As someone who has seen the power of this drug first hand, I urge you to not only consider the price, but also the mountain of clinical and anecdotal evidence that this drug lives up to its reputation.    Unfortunately, in the CF world, time is not a luxury that we enjoy.  I respectfully urge you to approve and begin marketing Kalydeco to those who need it immediately.  I would be happy to provide further detail and/or documentation of the claims made in this letter.   It has been such a life-changing miracle for us, that my husband and I are flying across the U.S. to attend the NACFC in Orlando next month.  Shaking hands with the Vertex team that developed Kalydeco is going to be one of the most memorable, intense moments of my life!

We haven’t seen any negative side effects of Kalydeco.  We have regularly tested Brady’s liver enzymes and they have remained stable and within the normal range.  The positive side-effects of Brady beginning Kalydeco have included: more energy, more restful sleep, restored sense of smell, complete disappearance of serious nasal polyps,  increased appetite, increased rate of growth, fewer digestive problems, reduced breathing treatment time, reduced airway clearance time, no further need for antibiotics or steroids, and much more normally functioning organs.  Those who love Brady have experienced a huge reduction in stress and anxiety.  We now have the ability to look toward the future, and an endless gratitude for modern medicine.  It is absolutely critical to get Kalydeco to those who need it in the timeliest manner possible.


Rebecca Schroeder, Mother of Brady Schroeder age 5."
I think it is pretty clear that I am a Kalydeco "super fan"!  I'm already buzzing with excitement for the NACFC next month!  Look for some exciting blog updates!

Sunday, July 22, 2012

Tricks of the Trade

Originally, I started this blog to document the experience of getting Kalydeco to Brady.  Now that Brady has been taking it for 5+ months and is doing so great, I don't have too many new exciting changes to report (boring is so AWESOME!)...so I'm going to have to expand the content of my blog a bit if I want to keep writing!  

Recently, two families with newly diagnosed infants with G551D have contacted me with a few questions about CF and Kalydeco.  It feels like such an enormous privilege to be able to help those people through such a scary time.  Of course, I get to try to explain to them how lucky they are to have been given that G551D, because right now that is like the golden ticket in the CF world.  But also, I get to simply help them understand this new CF Club they have unwillingly become a part of.  This blog is dedicated to "the newbies" and anyone else who just wants to know some of the tricks of the trade I have learned to make CF life healthier and easier :).  These are my top 10 "secrets of the pros" that I wish someone had told me about when Brady was diagnosed:

1) Invacare Mobilaire 50 psi compressor. Insurance might not cover this compressor, but I swear it is worth every penny out-of-pocket.  We bought this bad boy when Brady was about 9 months old and it is still going strong today (Brady is almost 5).  I love the adjustable pressure feauture, because you can crank it full blast for meds that are not "dose dependent," and adjust the pressure appropriately for other meds that you want to nebulize more slowly to get the maximum dosage out of.  It is more powerful (higher psi) than smaller less expensive models and actually blasts medicines into smaller particles, allowing drugs to reach the smallest of airways (*Side note, this is the compressor recommended by Genentech for use with Pulmozyme). http://www.pulmozyme.com/taking/treatment.html.  The best thing about this compressor is that it will allow you to nebulize medicines FAST and will cut treatment time for most meds.  When you have a baby or toddler getting used to treatments...reducing the time it takes can be HUGE!  I give this compressor two big "thumbs up" and if it ever breaks down, we will likely buy another one to replace it!  We ordered ours online and I've seen them range in price from about $250-$315 or so.  http://www.allegromedical.com/respiratory-therapy-c534/mobilaire-50-psi-compressor-p551975.html

2) Omron Micro Air.  Treatments are a part of life with CF.  Why not make them as easy as possible?  We just recently acquired this handy little device for treatments on-the-go and so far I'm impressed!  It takes 2 AA batteries to operate and uses a new "vibrating mesh" technology to break medicines into a fine mist.  It is seriously almost SILENT when it is nebulizing a medicine!  We used it on our recent camping trip and it was really awesome to watch Brady sit shirtless and do his treatments in the woods!  I can't comment on the durability yet, because it is still new.  I like having this device around and wish we had gotten it sooner! 
3) Philips Avent iQ24 Steam Sterilizer and Germ Guardian
There are lots of different ways to keep your nebulizer equipment clean.  This is how we do it.  First, wash the neb parts in warm soapy water (I use a clean paper towel to wipe down parts), rinse well, and then place them in the electric steam sterilizer http://www.amazon.com/Philips-AVENT-iQ24-Steam-Sterilizer/dp/B001C3MHF0.  It takes 6 minutes to sterilize.  Then I move the neb parts to the Germ Guardian, http://www.onestepahead.com/catalog/product.jsp?productId=487759 which uses dry heat to kill germs and as a side-effect, quickly dries the nebulizer parts with hot air.   **Always make sure to handle nebulizer parts with freshly washed hands!!  After the parts are dry, I toss them in their special tupperware in the cupboard.  Voila!  Clean and ready to use again!

4) Power Inverter for Car
We recently got a power inverter installed in our vehicle and I wish we had done it a long time ago!  Power goes out--no problem!  You can still do treatments in the car!  Travelling and don't want to stop for an hour and find a place to do treatments?  No problem!  Do your treatments en route.  We bought our inverter and cables online and had a local stereo shop install it for us.  We got this inverter:  http://www.theinverterstore.com/1250-watt-power-inverter.html  You have to order the cables separately.  It is also pretty handy to have a power source in your car when you need to plug-in the air pump to inflate your camping mattress or water toys at the lake :).

We had our inverter installed under the driver's side seat, so the plug-ins are easily accessible for Brady to do his treatments in the backseat while we are travelling.

5) Hand Hygiene
This is the #1 way to prevent the spread of germs and I can't underestimate the value of maintaining really good hand hygiene for your CFer.  For us, this means that I pack hand sanitizer in my purse and use it frequently when I'm out and about.  I use my own pen rather than the one at the counter.  I keep hand sanitizer in the door of my car and use a bit everytime I get back in the car from being in the grocery store etc...  In our house, we wash everytime we come in from being outside (playing, running errands, whatever).  I installed paper towel dispensers in the kitchen and bathrooms in my house.  Hand towels remain damp for long periods of time and get used by everyone.  They are bacterial traps and we don't use them.  Using a clean paper towel to dry your hands and then throwing it away is a much more effective way to keep germs from getting around.  I found a company that makes a less industrial looking paper towel holder and I buy paper towel refills at Costco.  http://brickhousedispensers.com/

6) Home Hygiene
I realize that many of the bugs that can affect CFers are ambient in our environment and cannot ever be completely eliminated.  With that said, there are many things you can do around the home to reduce the concentration of the most harmful bacteria and reduce the spread of viruses.  Brock and I team up for our cleaning routine every single weekend.  For us, cleaning is less about tidying up and more about killing!  Our weekly routine includes:

*Wipe down all doorknobs, kitchen cupboard handles, lightswitches, cell phones, remote controls, and any other frequently touched items with a disinfecting wipe.

* Vacuum carpeted areas with our UVC vacuum (UVC is a wavelength of light that kills bacteria, viruses, mold spores, and dust mites upon exposure).

* Steam clean our hardwood and ceramic tile floors with the trusty Steam Shark (steam mop). I love cleaning with UVC and steam because no chemicals are involved and there is no irritating smell left behind. 

*Clean showers and sinks frequently (any place that remains wet for longer periods of time is going to be a bacterial "hot spot").  It might be worth paying some special attention to your showerhead with a bleach/water soak every few weeks. http://www.boston.com/news/nation/articles/2009/09/15/bacteria_in_showerheads_may_be_harmful_study_finds/  It is extremely important to follow package instructions on cleaning products for appropriate disinfection.  Products that are not left on long enough or applied in the appropriate concentration can actually contribute to bacterial resistance. 

*We wash Brady's clothes, bedding, and towels in HOT water.  Laundry can be another unexpected source of bacteria.  It is important to move wet clean laundry to the dryer right away after washing, and dry completely.   http://abcnews.go.com/Health/Wellness/washing-machines-loaded-bacteria-dirty-clothes/story?id=10751420

*No shoes in the house.  We remove our shoes at the door to avoid bringing germs and bacteria into the home via the bottom of our shoes.  We ask our guests to do the same.  I keep a small basket of slippers and cozy socks by the front door in the winter so guests can keep their feet nice and warm. 

If anyone wants more detail on our cleaning schedule or UVC technology, I wrote a whole blog about it and even made a little video!  http://luckycfmom.blogspot.com/2011_04_01_archive.html

7) Smart Exposure
As much as I'd like to, I can't control the outside world.  I try to limit Brady's exposure to germs in public places with smart scheduling.  For example, I always make Brady's Dr. or CF clinic appts. first thing in the morning, when the waiting room isn't full of sick kids and the exam rooms haven't been recently occupied by patients.  In the middle of winter (cold and flu season), I don't take Brady with me to the grocery store during the busiest times of day, when the store is packed with people.  We schedule our trips early in the morning or on Friday or Saturday nights (when the rest of the world seems to have other/fun things to do!).  Our friends are fully aware of our "sick policy," which states that if you are currently ill...we don't want to hang out.  Let me stress that we DO NOT LIVE IN A BUBBLE.  I just try to make smart decisions about Brady's exposure and I think it has gone a long way. 

8) The Bravery Box
I keep a special box of toys and books to use when Brady has to undergo an unpleasant medical procedure like a blood draw.  I tell Brady what I'm offering (a book or little stuffed animal he has been wanting) in exchange for his bravery and holding still during the procedure.  Most of the time, he can't wait to get to the lab or wherever so he can get his reward!  The rewards don't have to be expensive, just whatever you know your kid will go the extra mile for!  The Bravery Box has made our lives so much easier and Brady typically feels really heroic and awesome after he successfully earns a bravery reward!

9) Praise Praise Praise Compliance to Breathing Treatments and Meds.
From the time Brady began breathing treatments at 6 mo. of age, we have tried hard to make treatment time special.  We pay loads of attention to Brady during this time--because every kid wants attention from their parents!  Brady gets to watch whatever he wants on TV during treatments and I usually sit with him and massage his legs.  Figure out what YOUR kid likes best and praise the crap out of them when they do things RIGHT!  It is so easy to wait until they start misbehaving or throwing a fit for treatments before you pay attention...but it is more effective to simply praise them when they are being responsible by taking all their meds and doing great!  We still give Brady a high-five and tell him how proud we are of him after every single treatment session!  Not only has it kept him healthy, it is a great confidence builder because staying compliant to treatments is hard work and he knows it! 

10) Don't Forget about Nutrition
Most CF patients visit with a dietician during clinic.  We know that our CFers need more fat and calories...but what about actual nutrition??  Doctors in Europe pay closer attention to the nutrition aspect of CF and encourage a "Mediterranean style" diet rich in healthy fats.  Here in the U.S., Doctors tend to focus more on quantity vs.quality of calories and food consumed.  The problem with this is that the CFers need more than just extra calories and fat--they also need more NUTRITION!  CFers struggle to metabolize fat soluble nutrients in particular--vitamins A, D, E, and K (hence the specialty CF vitamins).  A diet rich in antioxidants is vital to maintain good health for ANYONE and is particularly important for individuals with CF.  Brady isn't always cooperative with his diet, so I give him some antioxidant supplements to help fill in the gaps.  I try to focus on healthy sources of fat like those found in avocados, coconut, nuts, and seeds rather than relying on junk food filled with sugar and unhealthy trans fats.  We like JuicePlus Chewables (whole food gummies made with fruits and veggies) https://www.juiceplus.com/nsa/content/OtherProducts.soa.  I'm also a fan of the supplement NAC (N-acetyl cysteine) .  It is a powerful antioxidant that is most effective in the effervescent form sold by Bioadvantex (NAC is an easily oxidized compound.  Bioadvantex produces its NAC in an oxygen-free environment to preserve potency). http://www.bioadvantex.com/us/pharmanac.html  My husband and I are also big proponents of juicing fresh fruits and veggies.  We juice every day!  Brady still turns his nose up at our green juice blends...but I think adding concentrated nutrition to the diet through juicing would be beneficial to ANYONE--especially CFers! 

I hope people find some useful tips in this entry!  These are the things that have made our CF lives easier! Remember that this isn't necessarily the "right" way to do things...it is just what works for us!

Tuesday, June 19, 2012

Eye of the Storm

I can still feel CF swirling around me--like a devastating tornado.  I turn on my computer every morning and survey the damage.  Almost everyone in my CF circle does NOT have Kalydeco or any type of "miracle drug."  They are dealing with shitty old fashioned CF, that is a relentless and degenerative disease.  The more time that passes, the more perspective I'm able to gather on what is happening for Brady and our whole family right now.  Brady saw his CF specialist last Thursday.  It has been two months since our last check-up and 4 months total since he started Kalydeco.  I want to continue summarizing his progress.  You can check out his April visit here: http://luckycfmom.blogspot.com/2012/04/new-brand-of-cystic-fibrosis.html

Cough: None

Weight: 48 lbs. Same as last visit.  I wish he had gained at least a little weight, but I feel pretty good about his growth in general.  Brady has a tendency to grow either up our out...but not both at once.  Plus, we live in Northern Idaho, and the weather has been bad for a long time.  We are finally getting some sunny days and Brady's activity level has gone WAY up.  Sometimes I swear that those Kalydeco tabs are laced with a tiny bit of crack cocaine because there has been such a noticable change in his energy level.  We also did some experimenting with his enzyme dosing, which is further explained below.  

Height: 44 1/2 inches.  He grew an inch and a half in the last two months!

Pancreatic Function: At the April clinic visit, we had decided to play around with his enzyme dosage to see if we were giving him the appropriate amount.  After a small reduction, Brady began to lose a bit of weight, so we decided to keep him at his original enzyme dosage (3 Zenpep with meals, 2 with snacks).  He hasn't been complaining of any stomach aches and his poo has been very "normal."  It doesn't appear that Kalydeco is going to do much for Brady in terms of reducing his enzyme needs.  His pancreatic insufficiency has always been severe.  His pancreas just stopped working one day, when Brady was a little over 2 weeks old.  He may still need enzymes, but I can say without a doubt that Kalydeco has offered him many other digestive benefits. 

Breathing Treatments and Vest: When Brady began Kalydeco on Feb. 10th, his schedule looked like this:

Baseline Morning: Albuterol and Hypersal via nebulizer followed by 20 minutes on the VEST.  Total time spent was about 45 min.
Baseline Evening: Albuterol, Pulmozyme, and Hypersal via nebulizer followed by 20 min on the VEST.  Total time spent was about 50 min.

After 4 months on Kalydeco, his treatment schedule is now:
Morning: Twice a week (Monday and Thurs) we do Albuterol and Hypersal in the morning via neb. We are in the process of weaning Brady completely off Hypersal.  It is incredible to me that we used to do this treatment 14 times every week and now we are down to 2 times a week.  Our plan is to continue twice a week Hypersal for a month, then drop to once a week Hypersal for another month...then DONE!  We will continue to use Hypersal if Brady is sick, but we no longer feel like he needs this for maintance.  Brady continues to use his VEST every morning, but the time has been reduced from 20 to 15 minutes.  So now, there are 5 days every week where we wake up and do NO nebulizer treatments.  15 minutes on the VEST and he is done!  It is barely enough time for me to cook his breakfast!  It feels like we have so much extra time in the morning!
Evening: Another change that happened at the last clinic visit is that we have started using "The Vortex" (a holding chamber with a mask attachment) device with a regular Albuterol inhaler, rather than nebulizing Albuterol.  http://www.pari.com/products/holding_chambers/product/detail/info/smarttouch_pediatric_vortex_masks.html
When Brady wakes up from his afternoon nap, I give him a couple of puffs on the Vortex (just takes a minute).  He eats a snack while he wakes up and then does his Pulmozyme treatment via nebulizer followed by 15 minutes on the VEST.  Total treatment time in the evening is about 22 min. vs. the 50 min. we used to spend each night.

Other Oral Meds: Holding steady.  We haven't dropped any of his other meds. 

Sinuses: Kalydeco seems to have completely resolved Brady's previously serious sinus issues. 
Baseline: Brady had undergone 1 sinus surgery and did a round of oral Prednisone every 6-8 weeks to manage his polyp growth.  He also did steroid rinses for his sinuses 3 times every day using a device called the Nasatouchhttp://www.sinusdynamics.com/
Today: Brady's sinuses are clear and he is breathing freely.  His sense of smell has obviously returned, as he smells everything around him!  "Mom, smell this rock."  He NEVER used to comment on smells.  He hasn't taken any oral steroids in over 4 months now.  We also decreased and then eventually stopped all the steroid rinses also.  Today, we do NOTHING for his sinuses.  He stopped snoring after 3 days on Kalydeco and we haven't heard it since.  Brady's sinus issues had a real negative impact on his quality of life and the side-effects of Prednisone are less than pleasant.  To be completely free from this issue feels like such a miracle.  It is something we used to battle on a daily basis and now the issue is GONE.  We visited Brady's Ear/Nose/Throat Dr. a few weeks ago to document how well he is doing and the Dr. remarked that Brady's sinus tissues actually "look different" than before.  By the end of the visit, he was asking about Vertex stock as an investment opportunity.  I'd say he was pretty impressed! 

Mental Outlook: Before Kalydeco, I felt like I was swirling around in the dangerous winds of that tornado.   You feel so out of control and every once in a while you get flung into the side of a brick wall.  Going to clinic paralyzed me with fear. What new meds are they going to add?  Will I be able to get Brady to actually swallow/inhale/sit still through it?  What will his throat culture show?  Will his lungs be clear?  CF never rests and that means that you can never rest.  You have to fight CF CONSTANTLY.  It is so damn exhausting and wild rides make me sick to my stomach...

Today, we still have treatments to do and Brady still takes lots of pills, but it is eerily calm right here.  I can see the winds raging violently all around me...but it feels like Kalydeco has led us to the eye of the storm.  Life feels oddly light-hearted and non-eventful.  I have an enormous amount of appreciation for the little chunks of time we have been getting back over the last 4 months. I've replaced some of our morning treatment time with back massages (I've been trained in Massage Therapy and Brady has finally gotten wise to it).  In the evenings now, we spent more time playing outside because treatment time is so short.  An evolution of "normal" has taken place in our home. Kalydeco has been such a gift for all of us.  I calculated that Brady has ingested $105,264 (258 pills @$408/pill) worth of Kalydeco so far.  I'm so thankful that our insurance has decided that Brady is "worth it."  I feel like my experiences with CF and Kalydeco have allowed me to place my priorities firmly in the correct order and live my life accordingly.  And while I greatly appreciate the calm that the eye of the storm provides...I think we would all prefer that the storm would just GO AWAY ALEADY! 

Sunday, May 20, 2012

Response Guided Therapy

I haven't written much lately for several reasons:
1) The "On Par for a Cure" golf tournament for the CFF was May 11th, and was all consuming,
2) Nothing has changed with Brady, he is still holding steady at a level I would call "AWESOME," and I assume that people aren't super interested unless I have something important to say. 
3) My head has been a mess.   I want to preface this whole entry by saying: I am not a CF expert.  I am a stay-at-home mom of a 4 yr. old son with CF.  I happen to have a background in Chemistry and have learned a lot on my own about CFTR science.  This is all my opinion

Things are going great for Brady on Kalydeco.  What could I possibly have to worry about?
In some ways I am extremely happy.  I am on top of the world that Brady has Kalydeco and is doing as well as we had hoped, so why am I still laying awake at night?  Why do I feel so fortunate, yet so tortured at the same time?  I'm not going to dance around it and try to be politically correct, I'm just going to say it--THERE IS A MUCH LARGER POPULATION OF CFers THAT COULD BENEFIT FROM KALYDECO, BUT DON'T HAVE ACCESS TO IT.  Any CF patient who successfully transports any quantity of CFTR to their cell surface would respond to treatment with Kalydeco to some extent.  Researchers already know that this group includes:

*ALL gating mutations,
*Most Conductance mutations,
*Some splice mutations. 

The fact that the group of Kalydeco responders might soon be expanding is fantastic news!  I talk about mutation classes and what that means for CFTR transport in this blog: http://luckycfmom.blogspot.com/2011/11/mutation-matters.html Yet, all of us are painfully aware that Kalydeco has only been approved for G551D ages 6+ and it is extremely difficult or next to impossible to get insurance coverage for this super expensive drug "off-label." Furthermore, there is a growing body of evidence showing that in some cases, Kalydeco has been beneficial for patients who shouldn't theoretically show any response to the drug such as:

1)Heterozygous patients with class 1 and 2 mutations
Theoretically, From what we know about these mutations individually, there should be no CFTR on the cell surface and these patients shouldn't show a response to Kalydeco. 
In reality, I know of several cases of patients obtaining a script and coverage for Kalydeco "off-label," trying it, and showing reduction in sweat chloride and improvement in lung function.  I think some patients are having some CFTR reach the surface when their two CF mutations interact with one another through a process called Transcomplementation: http://luckycfmom.blogspot.com/2012/03/calling-all-heterozygotes.html

Almost everything you read about the DDF508 response to Kalydeco is that it DOES NOT work for this group. I want to very cautiously put this out there. 
Theoretically, there should be no surface CFTR to potentiate.  The vast majority of patients showed no significant response. 
In reality, a very small subset of DDF508 showed some response to Kalydeco in trials.  We are talking about 1 in 112 patients.  The scary thing is that they (researchers) have no idea how to identify one of these responders.  What makes them different from any other DDF508?? Still, right on the insert in every Kalydeco bottle it states that the drug is "not effective in patients with CF who are homozygous for the F508del mutations in the CFTR gene."  Is 1 in 112 patients statistically significant?  No.  Does that extremely rare DDF508 responder deserve the chance to find out if Kalydeco could help them?  Yes.

3)Who else?
The thing is, the biochemical reactions that take place within your body are as unique to you as your fingerprint.  We know that there is wide variability in the severity of CF, even between siblings or twins with identical genotype and similar environment.  There are other factors at play that influence CFTR.  I think Peter Mueller from Vertex was on to something amazing when he discussed idea this a few months ago. 
http://iom.edu/~/media/Files/Activity%20Files/Research/GenomicBasedResearch/2012-MAR-21/3%20-%20Peter%20Mueller.pdf  Take particular note of slides 31-37.  Doesn't that just blow your mind?  How awesome would it be to receive your own "Trial in a Box" from Vertex to track your body's response to Kalydeco and make a treatment decision based on the results?!  **This is not an official trial, or registered with clinicaltrials.gov.  This is an idea that is being talked about by those in the know...Vertex is definitely NOT recruiting for this right now.  It is just being discussed at a preliminary level.  The cooperation of the FDA and insurance industry would be of the utmost importance. 

Disclaimer --I just want to clarify that I am not suggesting that Kalydeco would work in every CF patient.  There are many CF patients that don't successfully transport any CFTR to the cell surface, and would not respond to treatment.  The point that I want to drive home is that:  NO ONE KNOWS FOR SURE IF IT WILL WORK IN AN INDIVIDUAL UNTIL IT IS TESTED IN THAT INDIVIDUAL.   

Response Guided Therapy
In an ideal world, when a drug like Kalydeco is discovered and found to be safe, people would be free to decide if they want to try it, and see if they feel better, or their sweat chloride drops.  If you show a response, then you would remain on the therapy.  If you didn't, they would know that you have no surface CFTR and you would stop and wait for the corrector + potentiator combo moving down the pipeline.  I mean, wouldn't this be revolutionary!  The problem is that this "trial in a box/trial of 1" design is not something that the FDA would look at as a valid statistical measure for approval.  That is why it is extremely important that the CF community continue to support the EXPERRT Act, which allows the FDA to bring in disease specialists for rare conditions like CF to best determine the endpoints for trials, etc...  The CF Foundation is truly blazing the trail toward a new generation of individualized, gene based medicine.  You can imagine that there are a few "norms" that we are going to have to challenge along the way.  Both Vertex and the CFF are legally bound to stay out of any off-label use because they are focued on obtaining wider regulatory approval in the U.S. and of course for our friends in Europe and Australia.  Waiting sucks.  I'm sure that Vertex would love nothing more than to fill thousands more Kalydeco orders and the CFF would love to see its community live longer and feel better.  Unfortunately, they have to play by the rules. 

I can't underestimate the importance of seeing the EXPERRT Act pass and become law because it would allow us to slightly change the rules and persue more individualized approaches to treatment.  The repercussions for CF patients could be phenomenal.  Visit the CFF's advocacy tookit to read about the EXPERRT Act, and quickly and easily email your elected officials asking for their support.  We need to educate the FDA about the new ways we are individualizing treatment for CF patients and this will allow us to be heard!  Personalize your letter for the greatest impact!  http://www.cff.org/GetInvolved/Advocate/AdvocacyToolkit/EXPERRTAct/

Off-label Documentation
Brady is part of the National CF Registry and we have documented in detail the benefits of Kalydeco through both office exams and lab work.  Every off-label approval and documented success of Kalydeco will tilt the odds a little more in our favor for additional insurance companies to approve it for others off-label.  Remember when Pulmozyme was first approved by the FDA?  It was only trialed in kids age 6 and older.  Of course, Dr.'s soon saw its benefits and began prescribing to younger patients.  At first, the insurance industry pushed back, but after seeing it routinely prescribed and accepted by other insurance companies, everyone eventually just began covering it for younger kids also--OFF-LABEL! Even insurance companies can see that PREVENTING problems in CF is cheaper than FIXING problems once they have already occured and caused potentially permanent damage.   I realize that Kalydeco is dangerously high priced.  It raises an automatic red flag for insurance companies.  Our insurance told us that it happens for anything costing over $10K per month in their system.  They automatically required the "letter of medical necessity" from Brady's Dr. and a "pre-authorization."  I live with constant fear that our insurance company will change their mind about covering Kalydeco for Brady, so we have been seeing the Dr. frequently, doing lots of lab work, and making sure there is NO DOUBT that it is working wonders for him.  I order his 5th bottle on Monday!  I can hardly believe it! 

Back to why I can't sleep
The image from Breck's thoughtful and well-written blog just after Kalydeco was approved has never left my mind. http://bennettgamel.blogspot.com/2012/01/will-helicopters-return-in-time-for-us.html Everyone waiting...stranded on that rooftop with the floodwaters rising around them.  She said it so brilliantly.  This is how I feel as I see how Kalydeco has positively affected Brady, and also having the knowledge that it could be helping many more.

Scene Setting
The whole CF community is on a deserted island in the middle of the ocean.  We have run out of food and we are all starving and ill, especially our children.  We see a helicopter in the distance and all scream with hope and delight!  Help arrives directly over my head and drops down a message for me,

"Here is the food you will need to sustain your family for the next 4 years. I am going back to the mainland to build a boat.  I will sail here and rescue everyone in a few years.  There is one condition--you cannot share any of this mountain of nourishment with anyone else on the island. You must only feed your own family. We have a videocamera on the island and if you are caught sharing, all your food will be taken back."

Then they fly away into the distance.  Everyone is staring at me asking what the note says.  When they will be back?  What the hell??  Why did they send help specifically to you?  Do you know them?   I read everyone the note and they digest the news of several more years of waiting.  In the meantime, I can't help but feel relieved as I feed my starving child what he needs to survive.  BUT--If I look just a bit further, I'll see another child suffering and feel another Mother's heart breaking.  It feels so extremely gluttonous to have access to Kalydeco while others don't. It has been such a lifechanging miracle for us.  It just makes me sick to know that we live in a world where money determines whether people live or die.  Because it doesn't matter how well the drug might work in you.  What matters right now seems to be technicalities like: what mutation you have, how old you are, what country you live in, what type of insurance coverage you have, etc... NOOOOOOOOOOOO!!!  It just doesn't feel right.  I don't know how I'll ever rest.

I hope everyone writes in to their representatives in support of the EXPERRT ACT!  I want to see the day when the "trial in a box" is more than an idea...it is a reality!   So what do I do now?  Since my family has the nourishment it needs, we can work to build shelters for the others, care for them in their weakest hours, and relentlessly keep the rescue fire burning, in the hopes of attracting a less idiotic helicopter pilot.  I may not be able to share my nourishment, but I can share my energy and love.  In Breck's version, my family flies away on the helicopter to safety, leaving the rest behind.  In my version, and in my heart, I will never leave the CF Community.  The rescue fire will never go out on my watch.