Roadmap to a Cure: Part II--Leave No Mutation Behind

Today started out with the second Plenary session: Roadmap to a Cure: Part II.  The discussion was given by Dr. Bonnie Ramsey, University of WA School of Medicine, Seattle WA.  Dr. Ramsey is also the Director of the CFF Therapeutics Development Network.  She is extremely smart and we are all lucky she has dedicated her career to CF. 

Dr. Ramsey’s talk went into detail about how the CFF is working to “leave no mutation behind.”  She talked about what was learned in the process of getting a successful FDA approval for Kalydeco and how we can use that “roadmap” to guide us toward successful treatments for other mutation classes.  I mentioned in the day 1 summary that knowledge of your personal mutations and their functional class will be crucial to take advantage of genetic modifying treatments like Kalydeco.  In the spirit of discovery, it is important to mention that the CFF has a free program to identify unknown mutations in patients called MAP—The Mutation Analysis Program.  If you have a CF diagnosis, but only 1 known mutation, the CFF will sequence your genome for free and find it!  This is so incredibly important. Standard panels to screen for CF usually include the most common 23-26 mutations.  NONE OF THE OTHER GATING MUTATIONS (other than G551D) ARE INCLUDED IN THE SCREENING PANELS!  If you still have an unknown mutation, it could potentially be in the gating class, and Vertex has already applied to the FDA to expand Kalydeco access to these patients!  Imagine what a pleasant surprise it would be to learn that your rare unknown mutation has a gating defect and you could soon begin taking and benefiting from Kalydeco!!!  I hope everyone with an unknown mutation will take advantage of this. http://www.cff.org/LivingWithCF/AssistanceResources/MAP/ If you know your mutations, but are unsure of which class they fall into, you may find that information on http://cftr2.org/.  Another valuable explanation of mutation classes and their dysfunction can be found at  http://www.cftrscience.com/ I wrote a blog in 2011 about mutation classes: http://luckycfmom.blogspot.com/2011/11/mutation-matters.html Of course, the CF clinic team may also be able to offer information on this as well.    

CF mutations are divided into 5 basic classes based on the nature of CFTR dysfunction they exhibit.  Mutations within the same class have similar cellular dysfunction, meaning that if a drug shows a positive response with 1 mutation within the class, there is potential that the drug may be therapeutic to the entire class.  In general, class I, II, and III are associated with more severe disease manifestation because they exhibit little to no functional CFTR activity.  Class IV and V mutations are associated with milder disease—patients may be pancreatic sufficient or slightly lower sweat test scores.  In these two classes, there is a very small amount of at least partially functional CFTR on the cell surface.  There are over 1900 CF mutations that have been discovered.  You can imagine that it is going to be a complex task to address each and every one, but the experience with Kalydeco shows us that IT CAN BE DONE. 

Ivacaftor clinical trials taught us that when approximately 30% CFTR function is restored, many clinical symptoms can be ameliorated.  Kalydeco is able to reach this therapeutic threshold for all gating mutations.  I am hopeful that the FDA will give this a quick positive ruling.  Kalydeco monotherapy may also soon be extended to children 2-5 who have G551D or any gating mutation.  The KIWI study (Kalydeco study in ages 2-5) has officially completed enrollment.  This is a 24 week study and results are anticipated in the second quarter of 2014. 

The KONDUCT study is another phase 3 trial that is already underway, and tests Kalydeco in the R117H mutation.  Results of this study are expected by the end of the year.  Right now, Kalydeco is approved to treat about 4% of the CF population.  If the label is expanded to include all gating mutations and R117H, we can bump that number up to about 7% of CF patients being treated with a gene modifier.  I want to reiterate that these mutations were not selected to be the first to be treated—in contrast, they were treated first because they are the absolute easiest to correct.  These patients have CFTR sitting on their epithelial cell surface, just waiting for a small molecule like Kalydeco to come along and open that dormant CFTR channel.     

There is a major focus on "fixing" the DF508 mutation, which falls into class II.  Mutations in this class exhibit multiple, complex dysfunctions within the cell.  The CFTR protein is 1) misfolded, 2) thermally unstable (the protein is sort of “floppy” and often unravels at normal body temp), and 3) also exhibits a “gating” defect.  In other words, even if you were able to correct the folding and thermal instability, you would still have a CFTR protein sitting on the surface unable to open—like G551D and other gating mutations.  To restore any meaningful function, a combination of correctors and potentiators must be used.  Correctors are small molecules that target misfolding, instability, and trafficking to the cell surface (problems inside the cell).  Potentiators target the gating defect (inability to open and close properly), once the CFTR protein reaches the appropriate place in the cell (cell surface).  Lab studies have shown that multiple corrector compounds plus a potentiator like Kalydeco, may be needed to obtain the level of clinical benefit seen in with Kalydeco in gating mutations.  When you pair multiple corrector molecules together to target different problems within the DF508 protein, the amount of CFTR rescue is increased dramatically--up to 80% restored function (that is even BETTER than Kalydeco works for G551D patients!).  These multi-corrector combos are still a few years out though, and I am still very optimistic that we will see an FDA approval of a first generation combination like VX-809/VX-770.  There are 2 phase 3 trials moving forward right now examining optimal dosages and relative change in FEV1.  The hope is that within the next several years, a drug combination will be FDA approved to treat the DF508 mutation, which will hopefully translate to treatment for all of class II. Because 50% of the CF population is homozygous for DF508 and 90% of the CF population carry at least one copy of this mutation, an effective treatment for DF508 could benefit up to 90% of the patient population.  While the VX-809/VX-770 combo is currently only being tested in homozygous patients, there is the potential that many heterozygotes may also benefit to some extent from this combination. Remember, with Kalydeco and G551D, only one mutation is being treated.  Heterozygotes with one copy of DF508 should be hopeful about any combinations designed to treat double DF508--especially the second generation combos, which have proven to be significantly more powerful in their ability to rescue CFTR function.   

What about Class I nonsense mutations?  Last year, the Ataluren studies yielded some disappointing results.  They failed to meet their primary endpoint and found that there is a strong drug interaction between Ataluren and inhaled aminoglycosides (TOBI is this type of drug).  Patients who were NOT taking TOBI showed some statistically significant improvement on Ataluren (5.7% increase in FEV1), but those who WERE taking TOBI showed absolutely no benefit.  Last year, no one seemed willing to hypothesize on the future of Ataluren and I feared the antibiotic interaction problem might be too much to overcome.  This year, Dr. Ramsey announced that there PTC Therapeutics will be moving forward in an additional phase III study to test their drug only in patients not on Tobramyacin therapy. In addition to this study, the CFF has initiated new research to address this mutation class.  The CFF invested millions of dollars this year and enlisted big hitters like Pfizer to search for new molecules to treat Class 1 mutations.  I understand that the Ataluren results were extremely disappointing for many--but please know that book is not yet closed!  Not only is the search on for a brand new molecule to treat class 1 mutations, they are also screening compounds that are already currently FDA approved. There are already several other existing compounds that have been shown to promote translational read-through of the CFTR protein.  Imagine how much time could be saved if we didn't have to start at the absolute beginning, with a brand new compound!  All the human safety trials could be skipped and we could move right into end stage trials designed to prove the therapeutic effect.  Plus, it seems that there may still be a chance for Ataluren to turn out some positive data from this new phase III trial.  Class I--you have not been forgotten.  

OK, so we have a plan for treating Class I, Class II, Class III (Kalydeco), and many in Class IV mutations (Kalydeco monotherapy or corrector/potentiator combo).  This still leaves approximately 10% of the CF population with rare mutations, who may not fall neatly into one of these therapeutic classes.  Many patients in this remaining 10% may have an unidentified mutation (utilize the Mutation Analysis Program to find out!), and may discover that their unknown mutation DOES actually fall into a class with an available drug.  If not...there is still a plan.  Yesterday, I described some techniques that have been developed to obtain a patient's own tissues to utilize for testing.  Truly personalized drugs may need the answer for these patients.  With the ability to obtain patient tissues for lab testing, compounds can be screened for a therapeutic effect in that individual.  When an effective drug is discovered, patients would participate in a "trial of 1," where the patient serves as their own control for the study--response guided therapy.  The trial of 1 concept is already being used in Denver to test whether Kalydeco might be beneficial for certain heterozygotes with splicing or other rare mutations that produce some residual CFTR function.  The CFF won't stop until a treatment is developed for 100% of mutations, and they have a plan on how to make that happen.  I haven't even mentioned that there are other therapies in the pipeline that are NOT mutation specific--in the realm of "gene therapy," it doesn't matter what mutation you have.  Anyone with CF would benefit, no matter their genotype.   By this time next year, researchers in the UK will be ready to present their data on their huge gene therapy trial.      

Changing the course of the disease at a basic level is obviously an important area of focus, and could provide amazing opportunities for all patients--particularly young children/infants that are able to be placed on these interventions at an early age.  That doesn't mean that we get to forget about treating traditional issues like inflammation and infection.  

Advancements in Anti-microbials

After laying out the roadmap to eventually treat the basic defect in all patients, Dr. Ramsey then turned to other areas of development in treating CF.  First she discussed a new way of improving treatment of Pseudomonas infections. It has been found that there is an excessive amount of Iron in the CF lung that contributes to bacterial overgrowth and the formation of biofilms.  Iron is basically food for bacteria, which makes the CF lung a smorgasbord for organisms like Pseudomonas.  Trials are moving into phase 2 for a drug called Gallium nitrate, which is a molecule almost exactly the same size as iron. The idea is that when Gallium nitrate is administered, it can slip right into the place in the cell where the iron normally resides--replacing the iron.  This disables the bacteria and results in disruption of the biofilm, as well as better antibiotic penetration, and better infection control.  Want to know the other good news?...Gallium is already an FDA approved drug for other indications, and it is moving into phase 2 trials in CF patients now!  

MRSA infection is very common, especially among CF patients in the U.S.(vs. UK).  There has been some debate about how harmful MRSA infection really is, but studies have shown that patients chronically infected with MRSA live 6.2 yrs less than those who are not.  In other words, they are becoming more convinced that aggressive treatment of this infection is necessary, and 3 studies are currently open and recruiting patients!  If you are interested in participating in one of these trials, contact your CF center!  I recommend that everyone sign up for "Clinical Trial Alerts" on CFF.org to receive the latest and greatest clinical trial news! http://www.cff.org/research/ClinicalResearch/Find/ClinicalTrialAlerts/

Of course, you can also find information on clinical trials at http://clinicaltrials.gov/

They are also investigating ways to improve treatment for Non-tuberculous myobacteria.

Treating Inflammation

Inflammation is a big problem for CF patients.  Inflammation can cause cell death, and subsequently, those dead cells leave behind waste products that are harmful to lung tissue.  Neutrophil elastase is one of those waste products causing damage in CF lungs.  According to the Australian ARESTCF study, patients as young as 3 months old, showed elevated neutrophil elastase levels in their lungs (a way to measure the level of inflammation), even in the absence of symptoms.  In other words, it is a problem that starts early in life and progresses over time.  We currently have only one proven efficacious therapy for inflammation--high dose ibuprofen.  

Thankfully, there are some ideas for future studies.  They will be looking at compounds that might be able to "sop up" some of that damaging elastase in the lungs.  In addition, the CFF has launched a Strategic Planning Initiative to evaluate more potential areas of anti-inflammation research.  

My thoughts on Day 2: Brock and I attended workshops and symposium talks all day and there is a lot more to write about.  It has been a real challenge for me to find time for all the Conference sessions, physical therapy, schmoozing with the amazing folks in attendance, and writing the blog.  Basically, I don't sleep while I am here, and Brock has been so good to chauffeur me around in the wheelchair and put up with all my craziness.  I feel like I still have so much to report, but I have to wrap up for now...I have a dance to get ready for!  I apologize for the quality of some of these slides and hope they are all at least readable.  The funniest thing about being here is that I have been recognized by the tattoo on my left foot about 25 times, "Hey, I know that foot!"  No one recognizes my face, but my foot is pretty famous!  I can't believe that the Conference is almost over now, and I survived!  Stay tuned peeps, more to come tomorrow!

Stupid escalators!

NACFC 2013--Day 1

We arrived safely in Salt Lake City yesterday afternoon—wheelchair, blue lightning bolt crutches, and all.   Of course, I got the full pat down by airport security, but otherwise it was smooth sailing and a nice short flight.  Last night, Brock and I were able to enjoy a quiet dinner together (that doesn’t happen often enough) and meet with one of our favorite Docs for a drink.

The real action started this morning, with the first session of workshops.  Brock and I attended the first 2 talks from the workshop CFTR 2013.  For the DF508 mutation, there are several issues that cause the ultimate degradation of the CFTR protein, but the primary issue is protein misfolding.  To be functional, the CFTR protein must be folded in precisely the right fashion, assemble in the correct order, and be stable enough not to unravel at normal human body temperatures.  Researchers are racing to find ways to “fix” each of these issues in DF508.  The first talk I attended in this workshop was entitled:

Analysis of CFTR NBD1 Co-Translational Folding Mechanism Using a Novel Solid-State Fret Assay (try saying THAT 5 times really fast!)
Shishido, H.: Yang, Z: Skach, W.R. Dept. of Biochemistry and Molecular Biology, Oregon Health and Science Division.

This was a very technical talk, but basically, this research is focused on finding a precise way to measure how well the CFTR molecule is folding.  Understanding this folding mechanism and discovering accurate ways to measure CFTR folding could help researchers find therapeutic pharmaceuticals.  This research presented a newly developed technique (solid-state Fret Assay) that successfully measures NBD1 folding (nucleotide binding domain 1—a section of the CFTR molecule that is misfolded in DF508).  This technique is currently being adapted for high throughput screening of small molecules that interact with and stabilize NBD1.

The second talk in the workshop was entitled:

The Regulatory Insertion (RI) in NBD1 as a Target for the Stabilization of DF508 CFTR.
Akeksandrov, A.; He, L.; Cui, L.; Caldwell, R.; Dokholyan. N.; Riordan, J.R. Biochemistry and Biophysics, UNC at Chapel, Chapel Hill, NC, USA.

This talk dealt with another issue pertaining to DF508—thermal instability.  In healthy individuals without CF, the CFTR protein remains stable enough at human body temperatures to remain functional.  With the DF508 mutation, CFTR is unstable and tends to “unravel” at body temp. This research was focused on improving the thermal stability of DF508 by modifying a section of the CFTR protein.  They found a certain portion of the protein that has a destabilizing effect on the DF508 mutation.  When this section of CFTR (RI) is “immobilized” or deleted from the protein, thermal stability is restored.  This concept may not sound groundbreaking, but it represents a deeper understanding of the protein dysfunction, which could lead to therapeutic pharmaceuticals to correct those problems.

After this talk, we moved to a different workshop session called Innovative Approaches to CF Therapy where the effects of Ivacaftor were discussed.

The first talk we heard was:
Results of the G551D Observational Study: The Effect of Ivacaftor in G551D Patients following FDA Approval.  
Rowe, S.M., Heltshe, S.L., Gonska, T., Donaldson, S., Borowitz, D., Gelfond, D. Sagel, D.D., Khan, U., Hamblett, N.M., VanDalfsen, J., Joseloff, E. Ramsey, B., 1. UAB, Birmingham, AL, USA; 2. Hospital for Sick Children, Toronto, ON, Canada; 3. Univ. of North Carolina, Chapel Hill, NC, USA; 4. SUNY at Buffalo, Buffalo NY, USA; 5. Univ of Colorado, Aurora, CO, USA; 6. TDN, Seattle Children’s Hospital, Seattle, WA, USA; 7. CFFT, Bethesda, MD, USA.

This was an extension study of Ivacaftor that examined previously unstudied clinical endpoints, and I was really excited to hear their data.  The clinical trials that led to the approval of Kalydeco used lung function and sweat chloride as major endpoints.  The GOAL study looked at alternate endpoints such as changes in hospitalization rate, and changes in positive Pseudomonas culture.  Researchers found that patients on Ivacaftor therapy spent significantly less time in the hospital and also decreased their odds of a positive Pseudomonas a. culture by 35%.  These are phenomena that I have heard of in some Kalydeco users, but it is always nice to see the data and make it official!  Many people have questioned whether Ivacaftor could make eradication of infection possible—and now we finally have some proof.

After the morning session and lunch, Brock and I made our way to the Milestones II Campaign meet-and-greet with the executive staff of the CFF, then headed to the first Plenary session.  The Plenary sessions were streamed live this year, so some of you may have already seen this information!  Dr. Beall described 3 challenges that the CFF is stepping up to face:
1) Development of disease modifying drugs for ALL mutations
2) Access to new therapies—The BEST drug in the world is no good if patients don’t have access to it! There must be a balance.  We want to encourage biopharmaceutical companies to innovate and bring novel therapies to the market…but that innovation should come at a price that doesn’t restrict access to that new innovative therapy.
3) Maintain access to quality care for ALL CF patients.

While it seems that the majority of CF news is focused on the G551D and DF508 mutations, Dr. Beall offered assurance that the CFF's investment strategy is designed to “leave no mutation behind.”  The CFF now has partnerships with several major pharmaceutical companies like Pfizer and Genzyme.  I hope they can bring some compounds to the table in the next few years.
He also described the major strategic planning effort that has taken place over the last year to offer insight and solutions to problems faced by the CF community.  For example, our CF specialists should not be bogged down with hours of paperwork and prior auths in order for a patient to gain access to a necessary Rx.  I think I speak for everyone when I say it would certainly be wonderful to have a more streamlined process!  Sometimes I feel like insurance companies put all these hoops in our way because they are COUNTING ON us giving up.  The CFF is working on creative ways to remove this barrier and make the whole process easier for physicians as well as patients.  I have had the privilege of working on the strategic planning committee for patient adherence, and I know there are several programs in the works designed to help patients overcome the obstacles to adherence--whatever those obstacles may be.  Maintaining appropriate, quality care for all patients is a growing challenge due to the increasing size and special needs of the adult CF population (a great problem to have!). The CFF has established a task force to help them work toward solutions for issues specific to adult CF care. The overall message that I took from Dr. Beall's presentation at the Plenary is that the CFF cares about all aspects of care and understands that improvements in quality of life may come from avenues other than genetic modification.  While it seems that the CFF has its sights firmly set on clinical trials and the science of CURING this disease, they truly are working behind the scenes to make sure the needs of every CF patient can be addressed in a positive fashion by the Foundation.

The main speaker at the first plenary was Dr. Scott Donaldson from the University of North Carolina at Chapel Hill.  His talk was entitled: Restoring CFTR Function, Road to a Cure Part 1

Dr. Donaldson began by describing the term "cure"--which is to fully relieve a person of the symptoms of a disease or condition.  What does a cure for CF look like?  How will we know when we have arrived?  First, he went through a brief history of the advancements through the years that have led us to where we are today.  He described the detail in which we now understand CFTR function, and the combinations of correctors and potentiators that might take us much closer to that cure (no new information was given on the VX-770/VX-809 combination).  He then went on to describe which CFTR functions are essential and must be corrected to restore health: pancreas, intestine, and lung.


Then he launched into the detail of the dysfunction that CF causes in each of these organs.  In the pancreas, CFTR is found in the surface lining the ducts that secrete digestive enzymes into the small intestine.  When CFTR is dysfunctional here, thick mucus accumulates and blocks these ducts, leaving the digestive enzymes trapped inside the organ.  In essence, the pancreas begins to digest itself, rather than your food.  CF disease in the intestine develops much in the same way it does in the lung (impaired bicarb secretion and chloride channel function results in retention of mucus, bacterial overgrowth, and inflammation). In the lung, CFTR dysfunction also manifests as decreased airway surface liquid, impaired mucociliary clearance, and decreased pH (CFers are overly acidic--pH is too low).  He described how lungs that exhibit appropriate pH have superior bacterial killing power vs. the overly acidic environment in the CF lung.  Regulating airway surface liquid pH could be a therapeutic target in the future.

Dr. Donaldson went on to discuss the need for new and improved assays to prove clinical benefit in all these areas.  In other words, are there tests that could be developed to more accurately measure CFTR function?  There isn't a direct correlation between sweat test test and lung function, so it may not be the best clinical endpoint to use if we are trying to prove the benefits of new drugs.  I know several patients taking Kalydeco who haven't seen huge sweat test changes, but have still seen big improvements in lung function.  Perhaps their CFTR is working better than we imagine, but we are simply measuring the wrong thing!  One new method that was discussed was the use of intestinal organoids to measure CFTR function.  A biopsy from the patient's rectum would yield a personal tissue sample.  The intestinal tissue contains small "organoids" that are designed to swell and draw in water.  In contrast, the intestinal organoids exhibit reduced ability to swell in individuals with impaired CFTR function.  This new technique may yield a new/better way to measure CFTR function than the sweat test.  

Another new technique was discussed that also uses a patient's own tissues for testing.  A nasal scrape provides epithelial tissues that are then cultured and available for testing.  While developing new "tests" may not be as exciting as developing new drugs, these new techniques are going to be an absolutely crucial piece of the puzzle as we move into a new era of truly personalized medicine--where you are treated based on your personal physiological response.  Cool.  

At this point, Dr. Donaldson reported some of the data from the GOAL study (that extension study of Kalydeco that I reported a bit on earlier in this blog).  In addition to showing reduced rates of positive pseudomonas cultures and reduced hospitalizations, the study also revealed that patients taking Kalydeco were able to normalize pH in the gut.  He described the ideal pH range for enzymes to be effective and hypothesized that this is part of the reason why patients taking Kalydeco have seen weight gain and better absorption.  The overly acidic environment prevents enzymes from working properly in many individuals with CF (which is why most of them are on acid blockers).  The pH changes seen in the intestine of patients taking Kalydeco means that they are able to move to the optimal range for enzyme function.  

Dr. Donaldson also showed data on improved mucociliary clearance in both the whole lung and also in the peripheral lung--where disease often begins.  He showed this really cool video showing a patient attempting to clear their lungs, measured over 30 coughs.  In the untreated CF lung, very little clearance was seen.  In the CF lung treated with Ivacaftor, there was a dramatic difference in the ability to clear mucus in the entire lung.  Typically, lung clearance in the periphery can be very difficult once small airways are blocked.  Because Kalydeco is a systemic therapy, it can reach tissues inhaled therapies couldn't, and have a greater impact on the small airways.  

Finally, he discussed how we might improve moving forward.  He didn't give specific information on when the trial of Ivacaftor in 2-5 year olds might be completed, but he did remark that they have a good indication that the earlier you are able to start this type of therapy, the better the outcome might be.  Another way to improve on this would be to treat BOTH of a patients mutations (for example, Brady is G551D/DF508.  He may receive increased benefit from a future combination therapy vs. Kalydeco alone).  Lastly, we must continue the pursuit of better, more effective compounds.    

My Personal Views on the Plenary:  I know that many of you were able to view the live streaming version of this and I have seen that some are disappointed by the lack of detail in regard to mutations other than G551D and DF508.  What about the nonsense class?  What about rare mutations?  I understand the frustration.  I haven't heard a word so far regarding Ataluren.  Last year, I got the impression that the antibiotic interaction issue was going to be too significant to overcome.  I don't have confirmation of that, but I do know that the CFF has enlisted Pfizer to search for drugs to treat the nonsense class and other rarer mutations that may not fall into a therapeutic class treated by Kalydeco or a potentiator/corrector compound.  It is also important to remember that gaining a successful FDA approval and getting a new drug on the market is the first important step here.  For example, researchers have long known that Kalydeco will effectively treat all gating mutations, but they had to first conduct studies on the biggest group in that mutation class (G551D), and then work on expanding the label from there--which they are doing now.  I think a similar situation could play out for the Vertex combos.  If it is approved, it will first be for the double DF508 folks.  Once it is on the market, they can work on continued trials to potentially expand the label--but the double deltas are going to provide the most solid data that could lead to approval.  I am not trying to minimize the fact that this is going to take a while, but I just want to assure people that just because your mutation isn't listed on these slides, doesn't mean that there isn't something in development for you.  If you have a mutation in the same "class" as one with developed therapeutics, you may also benefit...but it may take a little longer for that approval. I can't stress enough the importance of knowing which class YOUR rare mutation falls into.  More to come later!  Headed to the second plenary session NOW!

Comparitive Analysis and Golden Ticket Syndrome

This summer has been so fantastic..I've allowed myself to get a little lost in it.  We are fully enjoying the time and freedom Kalydeco has given us, and it feels like the life I had envisioned before I ever heard the words cystic fibrosis.  There have been several occasions this summer where everything has felt so crazy easy. Packing for a vacation or camping trip no longer requires special coolers full of meds, or lugging around expensive heavy machines. When we get invited to have dinner with friends, we don't have to rush home early to save time for treatments--we get to stay and play.  Sometimes it is difficult to understand the true weight of the treatment burden, until that burden has been lifted and you are free to experience life from a different perspective.  Brock and I are both still in awe that this is really happening for our family.  It STILL seems a little too good to be real.  

Flashback--Jan 31st, 2012

Backyard of the house we rented in Buckeye, AZ

We had been vacationing in Arizona when the FDA approved Kalydeco.  Brady was just coming off another round of Prednisone.  His sinuses were getting really bad again, and were completely blocked by polyps. He couldn't breathe through his nose at all or smell anything.  We had an appointment scheduled with Brady's ENT when we got home, and we knew there would likely be another sinus surgery in our near future.  I used to lay in bed and listen to Brady snore and snort himself awake every night.  His sinuses made breathing so labored and noisy, that I could literally hear his EVERY BREATH.  I can't even guess how many sleepless nights I listened to him struggle, cursing cystic fibrosis with every fiber of my being.  I remembered the look of fear and confusion that filled Brady's eyes as the anesthesia wore off from his previous surgeries, and my heart was filled with bitterness at the thought of doing it again.  Then Kalydeco came into our lives...

A Comparison: Pre-Kalydeco vs. Today 

Brady took his first dose of Kalydeco on Feb. 10th, 2012--just over 16 months ago.

Weight Pre-K: 46 lbs.     Height Pre-K: 42 1/2 inches
Weight today: 52 lbs.     Height Today: 48 1/2 inches
Brady didn't experience the huge weight gain that some do when starting Kalydeco.  His growth has always been at the top of the charts and he continues to be large for his age.

Sweat Test:
Pre-K:                      105 mmol/L
After 20 days on K:  48 mmol/L
After 6 mo. on K:     17 mmol/L
After 1 year on K:    27 mmol/L
Without a doubt, Brady has experienced a huge drop in sweat chloride levels.  It is interesting to me that the number has bounced around a little.  Not even the experts have been able to explain why, but my theory centers around Kalydeco's property of fat solubility.  Since Kalydeco is a fat soluble compound, it must be taken with dietary fat, so it can be "dissolved" within that fat and absorbed by the body.  For a CF patient to properly absorb fat, the meal must also be taken with the appropriate dosage of enzymes...or the fat will pass through the body unabsorbed and take the dissolved Kalydeco along with it.  Right after Brady started taking Kalydeco, he experienced a lot of changes in his digestive function and we experimented with lowering his enzyme dosage.  We finally decided that while his digestion had improved, he still needed similar enzyme levels.  We gave him a little dosage bump just prior to his 6 mo. post Kalydeco test.  I think the lowest sweat test score (17 mmol/L) is reflective of an ideal absorption situation where Brady was getting the most out of Kalydeco because of proper fat and enzyme dosage.  That is my theory until I hear evidence to convince me otherwise.  Of course, many of you know that dosing enzymes appropriately isn't an exact science and can be difficult for even the most savvy caregivers--especially since enzyme needs are constantly changing as kids grow.    

Breathing Treatments:
Pre-K: Morning--Albuterol followed by Hypersal and Pulmozyme via nebulizer (approx 45 min).
            Evening--Albuterol followed by Hypersal (approx. 35 min.).

*Brady followed this twice daily Albuterol/Hypersal and once daily Pulmozyme regimen as maintenance--more treatments would have been added during any viruses or exacerbations.

Today: Brady is VERY SLOWLY tapering off his last remaining breathing treatment--Pulmozyme. First, we moved to 1 Pulmozyme treatment, every other day for a month.  After that, we did Pulmozyme once every 3 days for a month.  This month, Brady is doing 2 puffs of Albuterol with a Vortex Spacer followed by a vial of Pulmozyme once every 4 days.  That translates to just 7 (approximately 10 min) breathing treatments for the entire month of August.  There has been a HUGE reduction in the amount of time Brady spends with a nebulizer.  We go to clinic at the end of this month and I don't see any reason why we won't continue to taper down from Pulmozyme until the treatments are GONE.  Brady has zero baseline cough, normal CT scan, and clean cultures.  We don't really have any indication that he needs Pulmozyme at all anymore, but we want to be especially careful and cautious about removing it--hence the ridiculously slow, controlled taper.

Airway Clearance
Pre-K: 20 minutes, twice daily on the Vest machine after breathing treatments.
Today: 15 min on the Vest once a day.
We only want to change one element of Brady's care at a time, so we are remaining focused on reduction in breathing treatments.  We might consider reducing/stopping Vest treatments in the future.

Sinuses
Pre-K: Aggressive sinus polyp growth.  Brady had a lot of upper respiratory inflammation and had his tonsils and adenoids removed in July of 2011. He had endoscopic sinus surgery in October 2011 to clear out the polyps.  Brady needed recurring bursts of Prednisone to manage the polyp re-growth as well as 3X daily steroid sinus rinses with a device called the "Nasatouch."  Brady absolutely HATED the treatments and we had to hold him down like a criminal to do the steroid rinses.  It sucked so bad.  Despite our aggressive efforts to slow the progression, the polyps had already re-grown to completely block his airway again by late January, 2012 and we were prepared to discuss another surgery with his ENT. For reference, Brady saw his ENT 11 times in the 6 months before he started Kalydeco.

Today: Brady has absolutely no sinus symptoms.  He doesn't snore at all and he seems to have completely regained his sense of smell.  We stopped the steroid sinus rinses long ago (well over a year) and he certainly doesn't need the constant bouts of Prednisone anymore.  For Brady, his sinuses were the issue most affecting his quality of life at age 4, and the symptoms began to disappear within DAYS of beginning treatment with Kalydeco.  We have only been to visit the ENT one time since Brady started Kalydeco, and the Dr. was amazed with what he saw.  He remarked that Brady's sinus tissues actually "looked" different to him and was thrilled that the symptoms had vanished.

Liver Enzymes
Patients taking Kalydeco are monitored for elevated liver enzymes with regular blood work. Brady's levels have remained within the normal range.


Sometimes at night, I open Brady's bedroom door and watch him sleep for a few minutes.  Silent, effortless breathing can be so very precious and beautiful.  Just a few days after Brady turned 6 (July 26th), Vertex Pharmaceuticals called us to get him enrolled in the patient assistance program. We learned that with our insurance and the patient assistance program, Kalydeco will cost us next to nothing next year.  Don't get me wrong, I am thrilled about this but....at the same time, I am nauseated by how easy Kalydeco is to obtain for some, and how IMPOSSIBLE it is to obtain for others (even if it might be just as effective for them).  Right now in the CF world, that G551D mutation is like a Golden Ticket for those who live in countries with access to Kalydeco.

This Golden Ticket doesn't involve a fabulous chocolate factory though.  I've found it feels more like this--

Scene From a Dream I Had Recently

The entire CF community is running from a pack of hungry lions. Everyone is screaming and running for their lives.  Randomly, a small number of patients are given a Golden Ticket, which instantly propels them to the very front of the running, screaming pack.  All of a sudden, there is a much safer distance between those lucky patients and the lions...but they are still running and scared.  Every time someone with a Golden Ticket turns their head to look back, they witness the beasts attacking the weakest, and sickest of the group--friends and loved ones.   

It is graphic and horrific.  It is unfair.  The Golden Ticket holders can't stop asking--Why was I chosen to be so lucky?  Why am I alive and ____ isn't?  They realize they could have easily been the next meal for the lions, but for some reason they were spared...at least for the time being.  

*Disclaimer--"Golden Ticket Syndrome" is something I made up.  I woke up with this scene in my head a few mornings ago after a dream.  I am not trying to imply that everyone with CF feels as though they are being chased by lions.  I am merely trying to illustrate how Golden Ticket Syndrome manifests itself in my fragile little mind.

Do I feel relieved that my baby isn't being devoured by hungry lions?--Of course. But I absolutely don't feel good either.  I have heard some version of Golden Ticket Syndrome described again and again by patients taking Kalydeco.  It is an awful mix of guilt, gratitude, sadness and fear.  I am so thankful that we were handed that Golden Ticket, but I can't stop running until all the lions are gone.

Epiphany

A lot has happened since my last blog entry.  Most importantly, I had an epiphany regarding Brady's health.  The path to enlightenment was a painful lesson for me, and unfortunately...for Brady also.  Let me explain. 

Missed Doses of Kalydeco and Standard CF Protocol
My last entry described what happened when Brady caught a stomach virus that led him to miss several days of Kalydeco.  He developed a cough as the stomach symptoms subsided, so we started him back on HyperSal treatments to help him clear junk out of his lungs (We had cut out daily HyperSal treatments months ago, as he no longer needed them for maintenance).  The cough quickly worsened.  It was a barky sounding "bronchospastic" cough that Albuterol wouldn't calm a bit.   After a few days of this, Brady's Dr. prescribed Augmentin and a burst of Prednisone to ease the inflammation in his lungs. The Prednisone helped immensely, but the cough didn't completely go away.  We stopped HyperSal for a few days (around the time I wrote my last entry), but restarted only a few days later after hearing a couple of suspicious coughs. 

Relapse
Once again, Brady's cough took a sharp turn for the worse and sounded exactly as before--bronchospasms. I couldn't understand what was causing this.  Had he acquired a serious lung infection that Augmentin hadn't touched?   Brady has had years of clean cultures...and has a CT scan showing NO VISIBLE LUNG DAMAGE...and a sweat test score well below the diagnostic level for CF.  What the hell?! I had a sick feeling in my stomach and was so confused about what was going on.  This time, Brady's Dr. requested a new throat culture, and started him on another short burst of Prednisone for the bronchospasms. 

As we waited for the throat culture results, I wracked my brain for answers.  I was a mess.  In my mind, I had convinced myself that if we could get Kalydeco to Brady while his lungs were still very healthy, that we might be able to spare him a lifetime of fighting lung infections.  Had I been terribly wrong?  Would he culture Pseudomonas or some other CF specific lung infection for the first time ever AFTER being on Kalydeco for 15 months?! 

The cough improved again with Prednisone, but didn't go completely away.  Brady's nurse called with the new culture results--NORMAL FLORA.  We were relieved, but still full of questions.  His Dr. wasn't sure what to do, but was anxious to see Brady return to baseline.   His recommendation was to start him on a different antibiotic for the cough.  Something wasn't adding up for me.  I didn't feel like the Augmentin had helped at all and I didn't think a new antibiotic was the answer either.  I didn't believe he had an infection at all!  Had he developed serious asthma?  Some kind of new allergy?

The Epiphany
I called my parents to share Brady's throat culture report.  Looking for answers, we retraced in detail the course Brady's cough had taken, and then it happened--I had an epiphany.   It hit me like a flash, and a punch in the gut at the same time.  I knew what was causing Brady's cough...and it wasn't an infection, asthma, or an allergy.  WE WERE CAUSING BRADY'S COUGH WITH THE HYPERSAL TREATMENTS!

As soon as I realized it, everything made sense.  Brady started HyperSal when he was 20 months old, and tolerated twice a day treatments with absolutely no problem and very little coughing... until he started Kalydeco.  We noticed his tolerance to HyperSal change quite a bit right after he began Kalydeco.  The treatment suddenly seemed a lot more irritating and produced more coughing than before it ever had before.  Because Kalydeco theoretically does the job of thinning mucous on it's own, we decided that HyperSal would be the first treatment to go.   It has been months since he has taken HyperSal, but I never dreamed his reaction to the treatment would be so dramatically different.  Before Kalydeco, we felt like Brady really NEEDED the HyperSal, and we considered it one of our greatest tools in fighting away CF bugs and coughs.  Had things really changed so much?

I thought back to Brady's first ever HyperSal treatment as a baby.  His Dr. made us trial it in the clinic, because it can be very irritating...and for some patients, can cause bronchospasms.  I remembered that patients in the clinical trials for VX-770 were not allowed to use HyperSal, but I had never heard an explanation for why it was excluded.  Yup, it all was all starting to make sense.  As this swirling realization came together in my head, my epiphany was quickly followed by nausea. 

What had we done?  Poor Brady.  The more he had coughed, the more HyperSal we gave him...because that is how you treat a CF cough.  We gave him antibiotics and Prednisone...because that is what you do to make a CF cough go away.  I was crushed thinking of all that time Brady spent coughing and all those drugs he swallowed for NO REASON!  Be gentle with me on the comments please, because trust me, I feel so bad for not realizing sooner and putting him through all that.

NEWS FLASH! 
Standard CF protocol isn't working for Brady anymore.  His biology is drastically different now.  This HyperSal incident was just the brutal slap in the face I needed to see that I can't rely on the same old line of thinking.   Numerous tests have shown us that Brady's body is working "normally."  In the CF world, doing treatments is how we protect and care for our children; it was so hard to grasp that my good intentions had gone so wrong.

Now I see
I realized that my overprotective instincts regarding Brady's health are not only unnecessary--they could be dangerous.  I realized that Brady didn't need a new antibiotic or steroids or MORE treatments to get well, he needed to be left alone to let his body heal on its own.  I realized that by stepping in and pumping up breathing treatments at the first sign of a cough...we had PROVOKED a health crisis in my sweet boy. I realized the answer was to stop treating him so much like he has CF and start treating him more like a regular healthy kid...because he is.  Jesus.  I drank wine and cried for a week after my epiphany.   

I called the CF clinic and explained my theory to them. 

Before Kalydeco, the HyperSal did precisely what it was designed to do--rehydrate dried out CF mucous.  After beginning treatment with Kalydeco, the mucous "buffer" in the lungs was no longer there for the saline to work on.  The saline went straight to the delicate lung tissues and caused considerably more irritation--so much that Brady can no longer tolerate Hypersal treatments at all.  His body is now violently rejecting something it used to need. 

Brady's Pulmonologist said it was a "fascinating theory," and gave us a few days to test it out before we went ahead with any more antibiotics.  Once we stopped HyperSal, the cough started to get better right away.  Now, Brady is totally back to normal and all is right with the world again.  Not only was Kalydeco working like it should...it was working better than my tiny little brain could even IMAGINE!  Since my epiphany, I've thought a lot more about other ways we might be "overmedicating" Brady, now that he is taking Kalydeco.  CF clinic is coming up this Thursday and I am anxious to talk to his Doc.   We are going to discuss all of Brady's drugs, whether his condition merits continued use, and come up with a systematic plan to bring him off the unneeded therapies, one-at-a-time.  I'm not going to just FREAK OUT and drop anything that he needs, but as we've seen, overmedicating can also have negative consequences.  I am certainly not suggesting that everyone taking Kalydeco stop doing any of their other treatments.   I understand that those who have suffered significant lung damage may still need many of their drugs and therapies to stay healthy, but Brady was only 4 1/2 when he started this game-changing drug and his case may be different.  I know all CF parents can relate when I say how extremely difficult it can be to make healthcare decisions for your child.  Now I understand that I might have to venture outside my "CF box" to do the right thing for Brady.

 

Dodging Bullets

In the interest of full-disclosure, I feel I need to give an update.  Something interesting happened since my last blog post—Brady got sick.  Let me preface this entry by saying that Brady has only had a few minor colds in his lifetime, and a case of Roseola as an infant, but has never had a serious respiratory exacerbation before.   Then, about a month ago, he got hit with a bad virus.  First, vomiting and diarrhea for a full 6 days.  Stomach bugs are no fun, regardless of the circumstances, but I was expecting the illness to run its course pretty quickly.  It didn’t.  This led me to an important question:

The Crisis

What the hell do you do when a patient is unable (for whatever reason) to take their Kalydeco orally?

During the course of the 6 day stomach bug, Brady missed several doses of Kalydeco.  Other doses were thrown-up after just a few minutes, and none of the doses were taken with an appropriate amount of fat (so very little drug was probably absorbed).  Brady was monitored closely by his pediatrician for dehydration and given Zofran to help with nausea.  As the days passed and the missed doses piled up, I began to see some of the symptoms of cystic fibrosis reappear in him.  When he began taking Kalydeco, the sinus inflammation/polyps shrunk within just a couple of days, and he was finally able to breathe through his nose.  After several missed doses of Kalydeco, I could hear the inflammation returning to his sinuses just as quickly as it had left.  Of course, I had to lick the poor kid’s forehead a few times to test for the characteristic “CF saltiness,” and to my horror, it also seemed to be returning.  All I could think about was getting him back on track with his Kalydeco dosing. 

Anecdotally, I have heard several older patients/adults describe their experience in “coming off” Kalydeco as extremely unpleasant.  Some say they can feel their chest tightening and feel that old “heaviness” with just a single missed dose.  The data shows that sweat chloride levels also suffer from a rebound effect when the Kalydeco is removed—shooting to all-time highs before returning to the normal baseline level. 

As Brady’s nausea began to fade, the cough started.  It appeared this virus wasn’t done with him yet.  The cough took ahold quickly and was the worst sound I have ever heard come out of him.  It was an uncontrollable, tight, barky sounding, unproductive cough.  Bronchospasms would wake him in the night and send him into coughing fits that sometimes ended with vomiting.  During Vest treatments, he would cough until he cried and begged to turn the machine off.  It scared me so bad.  After 3 days of CONSTANT coughing, he began a course of Augmentin and a 6 day burst of Prednisone to reduce the inflammation in his lungs.  The steroids helped tremendously with the bronchospasms, but he was still coughing a lot, and the sound had turned deep and phlegmy.   We decided to add Hypertonic Saline back into the treatment schedule, 2X a day, to help clear out the gunk.  The next few weeks brought gradual improvement, but were slow going.  He is finally almost back to 100% and we have dropped Hypertonic Saline again. 

By now you might be asking: “What’s the big deal”?  I mean, ALL KIDS GET SICK.  What is so extraordinary that I had to write a whole entry about this?  For me, this was a frightening experience on a number of levels.  First of all, watching Brady’s CF symptoms reappear was awful.  It illustrated for me what an extremely powerful drug Kalydeco really is.  Kalydeco has a short half-life and is metabolized quickly by the body, which is why timely dosing (every 12 hrs.) with appropriate fat (we shoot for 20 grams) is important to maintain levels in the bloodstream.    When levels in the blood drop and CFTR function turns off again, it doesn’t take long for ol’ shitty CF to come knocking.  It really throws the body for a loop.  I asked our CF Clinic Pharmacist if there was any way to administer Kalydeco via injection or IV for cases where a patient is unable to take the med orally and was told, “Not at this time.”  I don’t even know if that is possible, since Kalydeco is a fat soluble compound.

Also, this was the first bad respiratory bug that Brady has ever had.  I know many of my readers can probably relate when I say that listening to your little CFer cough causes both emotional and physical pain.  I mean, I feel an actual stab of pain in MY chest when HE coughs.  When your kid has CF, it becomes impossible not to analyze every cough, throat clearing, snort, or sneeze that comes out of them.  Unfortunately, a cough is rarely just a cough with CF, and can signify infection with some funky organism or worse.  I began to fear that Brady might end up in the hospital with this virus—something I didn’t think I would have to face once Kalydeco was onboard.  The reality is that Kalydeco may be able to lower Brady’s sweat chloride scores to a normal range, but he still has cystic fibrosis and is just a few missed doses away from his old problems.  Very humbling.  Missing those several doses probably put a big exclamation point on the respiratory symptoms caused by the virus, but the point is…HE GOT BETTER.  He didn’t end up hospitalized and I don’t believe he has an underlying infection.  The pediatrician told me he had been seeing a lot of this bad bug in his office, with the majority of kids presenting with symptoms similar to Brady’s. 

The Lesson

I think Brady just had a bad virus, and his symptoms were punctuated by missing Kalydeco for several days.  Because Brady is a complicated case (has CF, but also has Kalydeco normalizing his CFTR function), his Pediatrician consulted with his CF specialist several times.  Everyone (Brock and I, CF Doc, and Pediatrician) agreed that it was best to err on the side of caution and treat Brady a little more aggressively.  For me, this was a scary little glimpse into pulmonary exacerbations.  Of course, there is no way to know this for sure, but I feel like this virus could have led Brady to his first admission if he hadn’t been able to re-start Kalydeco just as the cough initiated.  It feels like we dodged a bullet.  It also broke my heart to get a little better taste of what many of my CF friends/families regularly endure (and I realize it was a mild, tiny taste).  The strength of this community is unparalleled. 

The Motivation

Brady recovered from the virus just in time for our recent trip to Boise, where I had been invited to speak at a CF education event.  As we packed our bags, I recalled all the lives that CF was currently interrupting.  I wondered how many trips had been cancelled, how many school functions had been missed, and how many sleepless nights CF families had spent because of CF.  I renewed my vow to work even harder and try to do more, because we have the luxury being healthy enough to do it.  I hope I chose the right words at the education event and made an impact on some of the families there.  The clinic team in Boise is really impressive.  One of the providers there, Dr. Perry Brown, is not only administering quality care to his patients, but working on a personal fundraiser to raise money for the CFF.  We all know how busy these Docs are, so I think it says a lot that he is committed to the community on this level.  We are lucky to have Docs like him and I encourage you to throw him a few bucks to help him reach his goal:   http://www.crowdrise.com/500milesforcysticfibrosis/fundraiser/perrybrown. 

I am currently in D.C. for a CFF strategic planning committee meeting on adherence and I fly home in the early a.m.  It has been rewarding work, but I am missing my boys.  I will be avoiding all moving sidewalks in the airport tomorrow…as a precaution.  Cheers to Vertex on their recent announcement of VX-661 combo data!  http://investors.vrtx.com/releasedetail.cfm?ReleaseID=757597 

The Light at the End of the Tunnel

It is time for an update. 

We have been super busy since returning home from Spain, but I know everyone is curious to know how Brady is doing after a year of treatment with Kalydeco, so here it goes.  He had CF clinic on Feb. 28^th.  Brady practiced PFT’s at this visit, but is still struggling with his technique (he is only 5, after all), so his numbers weren’t really meaningful.  His lungs sounded great though, and he has absolutely zero baseline cough.  Brady hasn’t gained a ton of weight, like many patients do on Kalydeco, but I am not worried.  He is extremely tall for his age, and has a slim build like my husband.  His energy level on Kalydeco is absolutely through the roof—I mean, he is like a different child (a child on crack cocaine!!).  We decided that we will perform another sweat test, mostly out of curiosity (his last sweat test was 17 mmol/L!  Amazing!).  The lab has been really booked up, but we hope to get in this week or next for the test, and I should have those results to report in my next entry. 

The big question on everyone’s mind is still—“What do we do now?”  Does he still need breathing treatments and airway clearance?  What about other oral meds like Prevacid, Ursodiol, and Singulair?  We decided to keep doing his only remaining breathing treatment—daily Pulmozyme, and once a day Vest treatment.  We agreed that everyone would feel more comfortable experimenting with coming off Pulmozyme after we are past cold and flu season.  I anticipate that we may move to Pulmozyme every other day at our next quarterly visit, and then maybe stop altogether if that goes well.  Honestly, I am really hesitant.  I know that he has a clean CT scan showing no bronchiectasis.  I know he has no cough and healthy lungs…but it is just so scary.  Doing treatments is how we “take care” of our kids with CF and I’ve got a real mental block about removing breathing treatments altogether.  I just want to do the right thing for him, so we are being very cautious.  After all, the goal is not to get him off all his meds—rather, to have him achieve his best possible health, and we feel really good about his health right now. 

We also decided to hold steady with his oral meds, but agreed that it is a topic to be revisited.  At last year’s NACFC, I saw evidence that patients taking Kalydeco were able to restore normal pH in their digestive system—meaning that Prevacid should no longer be needed.  Brady still takes pancreatic enzymes, but his overall digestive function has never been better.  No stomach aches and perfectly normal looking poops (this might be too much info for those outside the CF world, but my CF peeps can appreciate this for the miracle it is!). 

As a baby and toddler, Brady occasionally had elevated liver enzymes, which is why he takes Ursodiol.  We monitor his liver function regularly with blood work, and he has maintained normal function for close to 2 years now.  Kalydeco is metabolized by the liver, and some patients report elevated liver enzymes on the drug.  For those with severe liver damage, adding a drug like Kalydeco can really stress the organ, elevating those numbers.  On the other hand, patients with a minimally damaged liver might actually be able to improve their liver function, as Kalydeco thins the thick mucus clogging the organ’s ducts.  Brady’s liver enzymes have remained in the normal range and even improved slightly since beginning Kalydeco, so we see the potential to remove the drug in the future.  I know that there are studies ongoing right now to examine how Kalydeco affects organs beyond the lungs, so I would really love to see the results of that work before we remove Ursodiol.  I expect to see some data at the NACFC next fall.   

Additionally, we are all thrilled that Brady’s serious sinus issues still appear to be completely GONE.  We haven’t seen his ENT in almost a year, and he hasn’t needed antibiotics or steroids since he began taking Kalydeco.  This is a stark contrast to the constant cycles of Prednisone, and 3X daily steroid rinses he used to need to “manage” his sinus symptoms (and none of this worked anyway.  He was well on his way to needing his second surgical sinus clean-out at age 4).  I will never forget how amazing it was to watch Brady regain his sense of smell and begin breathing through his nose after only 3 days on Kalydeco.  Today, Brady continues to breathe freely through his nose.  He hasn’t snored in over a year, and still enjoys smelling anything and everything around him. 

Basically, it was a fantastic clinic visit!  We couldn’t be happier about Brady’s health.  Kalydeco is everything we hoped it could be AND MORE! 

Brady in his new "blue lightening" super hero cape!

 

As for me, I am staying plenty busy.  I am on the Great Strides Committee in Spokane, WA and like many of you, I am working hard to build my team and fundraise for the walk.  I’m also planning a wine event to benefit the CFF this spring.  I just returned home from my second CFF Adherence Action Team meeting in Washington D.C.  It really is such an honor to work with the amazing people on my team.   Next month, we will wrap up our work with one final meeting in D.C., and our recommendations will be presented to the Board of the CFF.  As a community, we are so extremely lucky to have The Foundation.  Working on this strategic planning committee has illustrated for me how much the CFF cares about every aspect of fighting this disease, far beyond simply funding drug trials.  

As a side note, I was a little embarrassed going into the meeting this time.  On my way to D.C., I performed a running face plant on a moving walkway in the Salt Lake City airport trying to catch my next flight.  I went down hard—breaking my fall with my left cheek, leaving me with an impressive “shiner.”  I also scraped up my left knee pretty bad.  Nothing boosts your confidence more than showing up to a room full of people you admire with a black eye! 

Looks "tough" right?

 

When our Adherence meeting adjourned at 5:00 p.m., I had a choice to make: go back to my hotel room to ice my face and knee, or take a cab to the CFF Volunteer Leadership Conference in Reston, VA—a 30 min. ride from my hotel.  I hadn’t registered for the Conference because I knew I would be busy with the Adherence meeting.  I went to my room for about 5 minutes, but it was absolutely killing me to sit there feeling sorry for myself, knowing that my CF family was so close by…so I grabbed a taxi and arrived at the Conference around 6:00 p.m. (fashionably late, just in time for dinner!).  Almost immediately, I knew I had made the right choice.   I managed to track down Dr. Beall fairly quickly, and landed myself a seat next to him that evening.  This is the second time I have invited myself to a CFF dinner reception, and I figure I am probably getting a reputation as a notorious party crasher!  That evening, the CFF honored the volunteers who work so hard to fund our search for a cure.  I was surrounded by my heroes that night—and I had to fight back tears every second of the reception (sometimes unsuccessfully).  Dr. Beall told me that he had talked about Brady in his speech earlier that day and I nearly choked on my salad when the “My Dream for CF” video that I had filmed for The Foundation in 2011 came up on the big screen at dinner.  I may have been a party crasher—but I felt like I belonged there that night.  After dinner, I got the chance to meet and greet so many more of my heroes.  Most of the time, I was introduced as, “the mother of the rock-smeller,” or “the tattoo lady.”  I had banged up my knee pretty badly with my flying leap at the airport, so I had on some ugly gray tights.  Several people requested (in their least creepy tone) that I please take off my tights so they could see my Kalydeco tattoo.  


The day I got my tattoo, which reads, "Honor the Gift" and features a small blue lightening bolt and the molecular structure of the Ivacaftor/Kalydeco molecule.  What's not to love?

After 3 or so glasses of wine…I gave in and let the ol’ scabby knee and unpedicured foot out to display the seemingly famous tattoo!  It is so funny to me that my left foot is my most recognizable feature!  I tried to personally thank as many people as I could that night and shared the details of Brady’s experience with anyone interested in listening.  My heart swelled with pride and gratitude that evening and I have never been more inspired, energized, and determined to keep working. 

My hope for everyone I met that night, and for everyone reading this, is that you can see the light shining at the of the tunnel.  I know fighting CF can feel endless, dark, and scary.  I know that every minute waiting for a miracle, is a minute too long.  CF is an unpredictable bitch of a disease and I wish so badly that the combo could be available immediately.  Sharing Brady’s story and progress is important to me because the hope for the future is real and that light at the end of the tunnel is shining brighter with each passing day.  It is exhilarating to see the Vertex combo moving into phase 3 with a newly granted “breakthrough” status that could allow it to come to market even faster than Kalydeco—which was one of the fastest FDA approvals ever!  Follow the link to read about what this brand new breakthrough status means:  http://www.pharmatimes.com/Article/13-01-09/US_FDA_announces_first_Breakthrough_Therapy_Designations.aspx

Keep moving.  The tunnel may be shorter than you think.  Can you see the light?