Let me preface this entry by saying that today I am feeling so tired, so I hope this makes sense. In other words, the day after day of being super excited and not sleeping or eating normally is catching up to this old lady. I am a pretty emotional person also, and the last few days have been quite overwhelming. About 10 o'clock this morning, I hit a wall and thought I was going to just pass out in the hallway...Fortunately, the very next presentation I saw was about VX-770 and apparently that particular subject works like crack for me. I see a big crash coming soon and as amazing as the last few days have been, I miss Brady, my husband, and my juicer. I don't have a lot of time to write before the closing events this evening so I'll jump right in.
Plenary session: Pulmonary Exacerbations
1st of all, the drug development pipeline has been updated and changed format on the www.cff.org website. It contains more information than ever before and I encourage you to explore the new, more interactive format. The pulmonary exacerbations talk first went into the difficulty of defining what exactly constitutes an exacerbation. They would like to establish a standardized method of identification and treatment among care centers. Currently, the protocol of treatment almost always includes a round of either oral or IV antibiotics. Seems logical, but data showed that in many cases, bacterial growth rebounded right back to pre-flare-up growth levels within a short time after treatment, even when FEV1 had increased, which begs the question: Is this the right course of action? They also addressed questions about how bacteria move or migrate throughout the airways. Do infections "slough" off one area of the lung and migrate to another? How do they spread and disperse? Also, which bugs (of the many they may see in culture) are the real trouble makers in terms of destruction of lung function? This talk presented a ton of questions, but not many answers. It was actually pretty surprising to me that so little is known about what causes pulmonary exacerbations and how to treat them. The speaker presented question after question about exacerbations and ended up with a slide that read exactly "We know a little more than Jack." As in, we know slightly more than jack shit about this and we need more studies. They have lots of ideas for learning more about this basic concept of risk factors that promote exacerbations and the most effective ways to treat them. They hope to learn from COPD exacerbation model and continued research projects are underway.
Next, I attended a talk about Key Advancements along the CF Drug Development Pipeline. They described what went wrong with Denufosol(an inhaled treatment that attempted to correct for CFTR dysfunction by activating an alternate channel (calcium channel) to transport chloride ions. In short, the trials were poorly designed and seemed to use some pretty creative statistical analysis to get as far as they did in trials. This talk felt sort of like an apology. Next up, they commented on where we are with Bronchitol. Bronchitol has already been approved for use in Europe, and is thought to have a similar line of function as Hypertonic Saline. Rather than inhaled salt, Bronchitol is a large molecule sugar alcohol that comes in the form of an inhaled powder(Similar to Advair, which saves a ton of time with a single inhalation vs. 30 or so min on neb with Hypersal). They plan to get this drug approved in the US soon, but they weren't sure when. They also couldn't comment on its efficacy above and beyond what is seen with Hypersal. In my mind, if it works as well as Hypersal but can be taken in a fraction of the time, it would improve quality of life enough to make it worth it. I'm sure we will be hearing more about this soon here in the US. This is where I hit that wall I mentioned earlier. Fortunately, next up was the data about VX-770. There was no new data, but rather a review of the trials that led to the FDA application. You would think that I would be getting used to seeing these stats by now, but something about those graphs on those huge projector screnes of dramatically dropping sweat chloride scores alongside similarly dramatic spikes in lung function put me in tears...again. It is nearly impossible to wrap your mind around a concept like this when you have been dealing with CF for any length of time. The more tired I get, the harder it is for me to control my emotions and act professional. I've been screaming on the inside the entire time I've been here and as I sat in that darkened room of completely subdued scientists and physicians...it was all I could do to keep myself seated and quiet. I wanted to stand up and give an old school fist pump and woot with each new graph displayed. I also wanted to kick the lady next to me because she didn't even seem to be paying attention. It just never ever gets old. My hands still shake and sweat, my breathing goes all funky, and I'm pretty sure my eyes bug out when VX-770 is the topic of conversation. I know getting VX-770 to where it is today has taken decades of collaboration between Vertex and the CFF, but it is truly is amazing that it was discovered at all. Dr. Beall told me yesterday that when they first began screening for compounds to treat the basic defect of CF, VX-770 was in one of the first few thousand compounds they screened. In the millions of compounds that they have screened since, nothing has come close to being as pharmacologically perfect. Imagine setting out to find a single burned out light bulb in all of Orange County and then finding it on the very first block you search. Finding that compound was more than lucky, it was a miracle. The last talk in this workshop was given by a researcher from Pfizer, one of the largest pharmaceutical companies in the world, who has now thrown themselves into the arena of CF small molecule research. Vertex now has company in searching for new and better functioning corrector compounds. Pfizer has its own databases of compounds that haven't previously been screened by anyone and they hope to find some gems there. They want to find the "next generation" of correctors that work specifically on the two misfolding sites I described on F508 yesterday. They believe that a two drug combo of correctors working synergistically will provide the best results and are setting out the find those burned out lightbulbs. Let's all hope they get as lucky as Vertex did, so they can begin the process of clinical trials...like NOW NOW NOW!
Next up was a special luncheon attended by CF patients, families, and certain caregivers. The face of healthcare is changing. Patients and providers can both do more to improve the quality of care, especially for chronically ill patients like those with CF. I didn't see this coming, but this talk hit me like a ton of bricks. "Tiffany Christensen is the CEO of Sick Girl Speaks, Inc. She was born with cystic fibrosis and has received two life-saving double lung transplants. Today she is a national public speaker, the author of “Sick Girl Speaks!” and “We are the Change: Transforming the Healthcare Experience through Partnership.” http://www.sickgirlspeaks.com
Yes, you read that right. She has undergone not one, but two double lung transplant procedures. It is amazing to me that she has spent most of her life very ill and close to death. There was so much life in that tiny lady that her body seemed too petite to possibly contain all the energy and positivity that she exuded. I'm planning an entire blog entry centered on the tools she taught about communication between patient and provider. I don't have the time to go into detail now as the closing event for the Conference begins in less than an hour, but I do want to say this. She described her drive to do something meaningful with her life as a way to "honor the gift." As soon as she said the words, tears sprung into my eyes and the words haven't escaped my mind for a second today. Honor the gift. She knows how lucky she is to have been given the gift of a second...and a third chance at life. She now works to train medical students, medical staff, and patients on how to improve communication in healthcare, especially in regard to end of life issues. Brady doesn't need a transplant, but VX-770 certainly feels like a gift to me. I'm not sure exactly how, but I will be spending the rest of my life trying to "honor the gift" I've been given through continued work and advocacy for the CF community. I'm so humbled I can barely stand how lucky I am. I have so much more to say, but I have am out of time for now. I fly out at 7:45 a.m. tomorrow morning.
Saturday, November 5, 2011
Friday, November 4, 2011
Coffee with Bob and day 2 of NACFC
Today started off with the second Plenary Session, entitled CFTR2. The CFTR2 project has a goal to identify and classify as many CFTR mutations as possible (they have close to 1900 different mutations identified now), and put that information into a database that can be easily accessed by both patients/families as well as researchers. Beyond simply identifying mutations, CFTR2 will attempt to offer more clinical information on what is known about each of those mutations. For example, some are associated with pancreatic sufficiency, or less severe lung disease. It will be a place to go to find out all about each particular mutation. This might not seem like much, but the CFF has worked hard over the years to gather extensive amounts of patient information through their patient registry program to be able to provide this type of clinical data correlated to mutation. As we are learning--mutation matters, so this will be a wonderful resource that should be up and running sometime next year.
Next, everyone went their respective ways to attend morning sessions. I decided to attend a talk about Gene Modifiers of CF Lung Disease. Studies have shown variability in lung function between siblings and twins, indicating that other forces may be at work in determining the clinical outcomes. Specifically, two sites on the chromosome were discovered to have significance in determining severity of lung disease. It was a very technical talk, but I will try to boil it down. One of the sites they found to be significant regulates cell death and the other site helps regulate the body's inflammation response. They hope to be able to learn how to manipulate functions at these crucial sites, so that therapies might be developed to correct for alleles associated with more severe lung disease. Understanding these types of modifying genes could help explain why two children from the same family can have drastically different "cases" of CF. As we know, inflammation plays a huge role in CF. Getting control over those inflammation genes would sure be nice...
I also attended a talk entitled: Antimicrobials in the CF Airways--How disease alters innate immunity. This was an interesting session that showed how loss of CFTR function impacts the normal defense mechanisms in the respiratory tract. Healthy individuals possess an "antimicrobial shield" that keeps the lungs from becoming infected. That shield is missing or impaired in individuals with CF. CFTR plays an important role in regulating airway surface liquid (necessary for mucociliary clearance). Impaired bicarbonate secretion alters the pH of that airway surface liquid. Lower pH reduces the "killing power" of the antimicrobials so that the body is unable to defend against something such as pseudomonas, which is an infection fairly exclusive to the CF pop. They are using pig and ferret animal models to study the primary effects of loss of CFTR and will continue that line of research.
Genetic Suseptibility for CF-related Diabetes Identified by Genome-wide Association. While there are similarities, CFRD is unlike type 1 or type 2 diabetes. Diabetes develops frequently in people with CF, occuring in 25-50% of adolescents and adults with CF. CF related diabetes develops over time as the capacity of pancreatic beta cells to secrete insulin declines over time. They used a continuum to explain how CFers can exhibit transient and significant drops in insulin sensitivity when ill or having a pulmonary exacerbation. In other words, it isn't a clear case of diabetic or not...it is more like diabetic while taking steroids or during a flare-up, and then a swing back toward more normal function when well. These swings between good function and bad function go on over time until the patient is chronically on the bad side, when interventions typically begin. The mechanisms of the development of CFRD are not well known, but several genetic markers have been located as risk factors in the development of type 2 diabetes(totally unrelated to CFTR or what genotype of CF you have). CF patients who also had these markers, were more likely to develop CFRD. With that information in mind, individuals with CF who have a family history of type 2 diabetes were found to be 3X more likely to develop CFRD than those who don't.
After lunch I attended my coffee meeting with Dr. Beall and the VP of Commications for the CFF, Marybeth McMahon. This time, I had my act together. They were both very interested in how issues are perceived within the community and what they can do to better address or educate about those issues. They wanted news from the inside. I spoke frankly about the impatience and worry over the success of the combination Vertex trials and the bittersweet nature of a breakthrough like VX-770 for people who won't benefit from this right away. They are acutely aware that time is of the essence and were genuinely interested in what they could do (besides hurry up with that damn cure!) to address the concerns of those still waiting. For me, this topic has caused me many sleepless nights. There is a certain amount of guilt that I just can't shake about having the child that will benefit first. But at the same time, I know that VX-770 will likely be a part of the treatment regimen for many mutations of CF (as they will require both corrector and potentiator compounds), so it is absolutely a good thing for everyone that it is approved. I think there is also a misconception that the F508 mutation has been put in the backseat while G551D has taken all the focus. As I will explain, the dysfunctions of the F508 mutation are numerous and complex. The G551D mutation is functionally, one of the easiest to correct for and VX-770 was discovered while screening millions of compounds with robots and supercomputers. It was not, by any means, an intentional snubbing of fixing the most common mutation...rather, a place to start. The "potentiating" action of VX-770 is a single piece of a larger puzzle for F508. I think it is an appropriate time to revisit the new information I learned yesterday about fixing F508. They now know that there are 2 distinct and separate problems that occur in F508 that cause misfolding of the protein. Misfolded proteins do not mature and travel to the cell membrane. If they only correct for one misfolding problem, they seem to top out at about 15% retrieval of CFTR function for F508 patients, which isn't enough to have clinical benefits. The good news is that they've shown that when both of these misfolding problems are corrected for in the lab, the two correctors work synergistically (the action of the 2 correctors together is greater than the sum of the two individually), producing the clinically significant outcomes we all want. Blah blah blah...So what does that mean for VX-809 and VX-661? I'm afraid they still aren't sure. From what I've learned since I've been here, I have a gut feeling that the VX-809/VX-770 combo alone won't be enough. A third compound (or different corrector) will need to be factored in to correct for the second misfolding site. This is just my opinion.
Highlights and tidbits: During our coffee today, Bob said "When VX-770 is approved in April...." He sounded pretty damn sure that next April is when it is all going to happen. I asked about the pediatric trial and he says it will not be placebo controlled, and of fairly short duration (3 months). This trial is about safety and appropriate dose for kids, not proof that it works. I asked him when it will begin enrollment and he promised to find out something more concrete than "sometime in 2012" and report back to me within the next 2 days. Then he invited me the dinner reception this evening for Conference Speakers and Fellows as his personal guest. That's right...it's a date. Naturally I accepted. He also went on and on about the book and how much he loved it. He even brought it to registration this morning to show his friends. He is very proud of it :) After coffee, I went to film "my dream for CF." I was so nervous. I hope I did alright. Of course, it rained here today so my hair was all funky. I'm sure that I'm leaving things out, but I will write more either tonight or tomorrow. Right now, I've got to get ready to meet my new boyfriend Bob for our date! Once again, sorry for the screw-ups, I'm trying to get this updates done FAST!
Next, everyone went their respective ways to attend morning sessions. I decided to attend a talk about Gene Modifiers of CF Lung Disease. Studies have shown variability in lung function between siblings and twins, indicating that other forces may be at work in determining the clinical outcomes. Specifically, two sites on the chromosome were discovered to have significance in determining severity of lung disease. It was a very technical talk, but I will try to boil it down. One of the sites they found to be significant regulates cell death and the other site helps regulate the body's inflammation response. They hope to be able to learn how to manipulate functions at these crucial sites, so that therapies might be developed to correct for alleles associated with more severe lung disease. Understanding these types of modifying genes could help explain why two children from the same family can have drastically different "cases" of CF. As we know, inflammation plays a huge role in CF. Getting control over those inflammation genes would sure be nice...
I also attended a talk entitled: Antimicrobials in the CF Airways--How disease alters innate immunity. This was an interesting session that showed how loss of CFTR function impacts the normal defense mechanisms in the respiratory tract. Healthy individuals possess an "antimicrobial shield" that keeps the lungs from becoming infected. That shield is missing or impaired in individuals with CF. CFTR plays an important role in regulating airway surface liquid (necessary for mucociliary clearance). Impaired bicarbonate secretion alters the pH of that airway surface liquid. Lower pH reduces the "killing power" of the antimicrobials so that the body is unable to defend against something such as pseudomonas, which is an infection fairly exclusive to the CF pop. They are using pig and ferret animal models to study the primary effects of loss of CFTR and will continue that line of research.
Genetic Suseptibility for CF-related Diabetes Identified by Genome-wide Association. While there are similarities, CFRD is unlike type 1 or type 2 diabetes. Diabetes develops frequently in people with CF, occuring in 25-50% of adolescents and adults with CF. CF related diabetes develops over time as the capacity of pancreatic beta cells to secrete insulin declines over time. They used a continuum to explain how CFers can exhibit transient and significant drops in insulin sensitivity when ill or having a pulmonary exacerbation. In other words, it isn't a clear case of diabetic or not...it is more like diabetic while taking steroids or during a flare-up, and then a swing back toward more normal function when well. These swings between good function and bad function go on over time until the patient is chronically on the bad side, when interventions typically begin. The mechanisms of the development of CFRD are not well known, but several genetic markers have been located as risk factors in the development of type 2 diabetes(totally unrelated to CFTR or what genotype of CF you have). CF patients who also had these markers, were more likely to develop CFRD. With that information in mind, individuals with CF who have a family history of type 2 diabetes were found to be 3X more likely to develop CFRD than those who don't.
After lunch I attended my coffee meeting with Dr. Beall and the VP of Commications for the CFF, Marybeth McMahon. This time, I had my act together. They were both very interested in how issues are perceived within the community and what they can do to better address or educate about those issues. They wanted news from the inside. I spoke frankly about the impatience and worry over the success of the combination Vertex trials and the bittersweet nature of a breakthrough like VX-770 for people who won't benefit from this right away. They are acutely aware that time is of the essence and were genuinely interested in what they could do (besides hurry up with that damn cure!) to address the concerns of those still waiting. For me, this topic has caused me many sleepless nights. There is a certain amount of guilt that I just can't shake about having the child that will benefit first. But at the same time, I know that VX-770 will likely be a part of the treatment regimen for many mutations of CF (as they will require both corrector and potentiator compounds), so it is absolutely a good thing for everyone that it is approved. I think there is also a misconception that the F508 mutation has been put in the backseat while G551D has taken all the focus. As I will explain, the dysfunctions of the F508 mutation are numerous and complex. The G551D mutation is functionally, one of the easiest to correct for and VX-770 was discovered while screening millions of compounds with robots and supercomputers. It was not, by any means, an intentional snubbing of fixing the most common mutation...rather, a place to start. The "potentiating" action of VX-770 is a single piece of a larger puzzle for F508. I think it is an appropriate time to revisit the new information I learned yesterday about fixing F508. They now know that there are 2 distinct and separate problems that occur in F508 that cause misfolding of the protein. Misfolded proteins do not mature and travel to the cell membrane. If they only correct for one misfolding problem, they seem to top out at about 15% retrieval of CFTR function for F508 patients, which isn't enough to have clinical benefits. The good news is that they've shown that when both of these misfolding problems are corrected for in the lab, the two correctors work synergistically (the action of the 2 correctors together is greater than the sum of the two individually), producing the clinically significant outcomes we all want. Blah blah blah...So what does that mean for VX-809 and VX-661? I'm afraid they still aren't sure. From what I've learned since I've been here, I have a gut feeling that the VX-809/VX-770 combo alone won't be enough. A third compound (or different corrector) will need to be factored in to correct for the second misfolding site. This is just my opinion.
Highlights and tidbits: During our coffee today, Bob said "When VX-770 is approved in April...." He sounded pretty damn sure that next April is when it is all going to happen. I asked about the pediatric trial and he says it will not be placebo controlled, and of fairly short duration (3 months). This trial is about safety and appropriate dose for kids, not proof that it works. I asked him when it will begin enrollment and he promised to find out something more concrete than "sometime in 2012" and report back to me within the next 2 days. Then he invited me the dinner reception this evening for Conference Speakers and Fellows as his personal guest. That's right...it's a date. Naturally I accepted. He also went on and on about the book and how much he loved it. He even brought it to registration this morning to show his friends. He is very proud of it :) After coffee, I went to film "my dream for CF." I was so nervous. I hope I did alright. Of course, it rained here today so my hair was all funky. I'm sure that I'm leaving things out, but I will write more either tonight or tomorrow. Right now, I've got to get ready to meet my new boyfriend Bob for our date! Once again, sorry for the screw-ups, I'm trying to get this updates done FAST!
Thursday, November 3, 2011
Prelude to a kiss
I am exactly where I belong. Today was one of the most amazing days of my life. My flight landed at 9:30 p.m. last night, but I was so pumped that I was up and ready by 6:30 a.m. this morning. I made my way to the Conference and sat through some interesting sessions today. Here is a brief summary of the sessions I attended:
Workshop: Novel Strategies for CF Therapy--The speakers in this workshop discussed topics including results of a clinical trial to test the anti-inflammatory properties of N-Acetyl cysteine (bioadvantex fizzy tabs). Clinical test showed a "protective" effect of orally ingested NAC against pulmonary exacerbations. They are interested enough in this data to proceed with further trials. The stats weren't mind blowing, but interesting.
Gene Therapy: I made a point to attend these workshops because I feel that it is an area of research that I know the least about. The first speaker addressed the gene therapy trials and success they have seen utilizing lipid-mediated gene therapy in mice. I realize the concept of gene therapy has been around for a long time. It seems like they have finally found a vector (method of delivery) with the lipid model that facilitates sustained gene expression that is well tolerated by the patient. Mice treated with nebulized therapy showed gene for extended periods, as well as changes in mRNA. The "lipid model" has already been tested in humans and the next presenter addressed safety and gene expression in humans with CF for his talk. They found that very low, repeated (monthly) doses of gene therapy gave the fewest side effects with the greatest translated gene expression. A larger study is planned to initiate soon, but funding was cited as a major obstacle to moving forward. I've been so focused on Vertex for obvious reasons, but it was great to hear about this potential "cure" continuing to progress.
CFTR: Fixing DF508
It is complicated business to correct the function of DF508. Today I learned that researchers have discovered 2 separate dysfunctions that cause misfolding of the CFTR protein for this mutation. Estimates show that approximately 20-30% CFTR function must be restored to get significant clinical benefits. So far, they seem to be hitting a ceiling with how much they can restore with ANY single corrector, including VX-809 (which they estimated restored 15% CFTR). I heard, for the first time ever, that they think it will take a combination of TWO separate correctors plus the VX-770(or another potentiator compound) to hit their goal of restoring function for this mutation. This DOESN'T MEAN that the correctors in trials aren't working...It means that it might take VX-809 + VX-661 + VX-770 for example, to correct for this mutation. After a full day of lecture, I am just as optimistic as ever about the advances being made to treat DF508. As I said before, it is much more complicated, but they are on it like "white on rice." The detail that they are able to describe the function of the CFTR protein is just dizzying. It is no longer a mystery, but simply a quest for the right combination of compounds. It was stressed many times that no assumptions should be made until further trial data is released. I hope I can report more about this tomorrow.
The Changing Face of the Infants with CF
This series of presentations highlighted the changes that have come about as a result of newborn screening and early intervention. The session entitled "CF Lung Disease-No Time to Waste" was a little scary. It basically showed statistical evidence(though CT scan) that lung disease begins to progress shortly after birth...even in the absence of symptoms. 20% of screened infants even showed early signs of bronchiecstasis in the absence of symptoms. This early damage to the small airways can be undetectable. What I took away from this workshop is: DO NOT WAIT UNTIL SYMPTOMS PRESENT TO TREAT THE CF LUNGS! Be proactive rather than reactive. By the time it is noticed through symptoms, significant damage is already done. If you are on the fence about starting treatments like Pulmozyme or HS Saline...don't wait. Just do it.
Here is where things start to get really exciting! After the classes today, all 4000 attendees came together for the 1st Plenary Session of the Conference. I arrived early and found the giant ballroom mostly empty...except for Dr. Bob Beall, and several other major players that I have only seen in educational webcasts. So I did what any good stalker would do. I planted myself about 3 rows behind him and stared and smiled weirdly at him for about 10 minutes. Finally, my excitement got the best of me and I launched myself at Dr. Preston Campbell. He quickly decided I should speak with Dr. Beall. He led me over and introduced me to him. I know that I squealed, covered my face with my hands, and jumped up and down before I threw my arms around him. This is not normal behavior for me. I hugged him hard, thanked him, and I think both Campbell and Beall cried a little bit too. Since people were pouring into the room, we didn't have much time. Somehow, within a span of about 15 minutes, I landed a reserved seat in the FRONT ROW DIRECTLY IN FRONT OF THE SPEAKER! I was seated right next to the Foundation big wigs and major donors. It was amazing and surreal to watch the next few hours unfold. The Plenary Session today was about the progress of the last 25 yrs in CF research. It was like music to my ears. I was lucky enough to meet some families in the CF community including Lindsay Shipp and her mother Barb. Lindsay has participated in the VX-770 trials...and is also an amazing singer/performer. She sang for us at the VIP dinner that I snuck into(thanks to Raven and Britt!). I'm so thankful for people like Lindsay, who have done so much to pave the way. Not to mention that she was just a beautiful little firecracker that lit up the room. The VIP dinner was attended by only 117 of the 4000 attendees, so there were some important people there. I heard that Bob was talking about me at his table, so we decided it would be a good time to give him the book of pictures and letters from all of us. THIS IS WHEN I KISSED HIM! 3 times I think. We took pictures and he was very appreciative. I thought it couldn't get much better until later in the night, right before I left he told me, "In all my years, this is the most thoughtful, nicest gift anyone has ever given me." I just about lost it. For those of you that contributed, please know that he loved it for real. I decided I'd better get out of there so I could cry it out in private. All happy tears. Surreal, overwhelming happy tears. My coffee meeting with Bob was changed to 2:00 tomorrow afternoon and I learned that I will get the opportunity to film a "my dream for CF video" for the Foundation also. The absolute only way that today could have gotten any better is if my shoes were more comfortable. Please excuse any typos or errors. It is very late and I'm exhausted. More tomorrow. Can you feel me smiling?
Workshop: Novel Strategies for CF Therapy--The speakers in this workshop discussed topics including results of a clinical trial to test the anti-inflammatory properties of N-Acetyl cysteine (bioadvantex fizzy tabs). Clinical test showed a "protective" effect of orally ingested NAC against pulmonary exacerbations. They are interested enough in this data to proceed with further trials. The stats weren't mind blowing, but interesting.
Gene Therapy: I made a point to attend these workshops because I feel that it is an area of research that I know the least about. The first speaker addressed the gene therapy trials and success they have seen utilizing lipid-mediated gene therapy in mice. I realize the concept of gene therapy has been around for a long time. It seems like they have finally found a vector (method of delivery) with the lipid model that facilitates sustained gene expression that is well tolerated by the patient. Mice treated with nebulized therapy showed gene for extended periods, as well as changes in mRNA. The "lipid model" has already been tested in humans and the next presenter addressed safety and gene expression in humans with CF for his talk. They found that very low, repeated (monthly) doses of gene therapy gave the fewest side effects with the greatest translated gene expression. A larger study is planned to initiate soon, but funding was cited as a major obstacle to moving forward. I've been so focused on Vertex for obvious reasons, but it was great to hear about this potential "cure" continuing to progress.
CFTR: Fixing DF508
It is complicated business to correct the function of DF508. Today I learned that researchers have discovered 2 separate dysfunctions that cause misfolding of the CFTR protein for this mutation. Estimates show that approximately 20-30% CFTR function must be restored to get significant clinical benefits. So far, they seem to be hitting a ceiling with how much they can restore with ANY single corrector, including VX-809 (which they estimated restored 15% CFTR). I heard, for the first time ever, that they think it will take a combination of TWO separate correctors plus the VX-770(or another potentiator compound) to hit their goal of restoring function for this mutation. This DOESN'T MEAN that the correctors in trials aren't working...It means that it might take VX-809 + VX-661 + VX-770 for example, to correct for this mutation. After a full day of lecture, I am just as optimistic as ever about the advances being made to treat DF508. As I said before, it is much more complicated, but they are on it like "white on rice." The detail that they are able to describe the function of the CFTR protein is just dizzying. It is no longer a mystery, but simply a quest for the right combination of compounds. It was stressed many times that no assumptions should be made until further trial data is released. I hope I can report more about this tomorrow.
The Changing Face of the Infants with CF
This series of presentations highlighted the changes that have come about as a result of newborn screening and early intervention. The session entitled "CF Lung Disease-No Time to Waste" was a little scary. It basically showed statistical evidence(though CT scan) that lung disease begins to progress shortly after birth...even in the absence of symptoms. 20% of screened infants even showed early signs of bronchiecstasis in the absence of symptoms. This early damage to the small airways can be undetectable. What I took away from this workshop is: DO NOT WAIT UNTIL SYMPTOMS PRESENT TO TREAT THE CF LUNGS! Be proactive rather than reactive. By the time it is noticed through symptoms, significant damage is already done. If you are on the fence about starting treatments like Pulmozyme or HS Saline...don't wait. Just do it.
Here is where things start to get really exciting! After the classes today, all 4000 attendees came together for the 1st Plenary Session of the Conference. I arrived early and found the giant ballroom mostly empty...except for Dr. Bob Beall, and several other major players that I have only seen in educational webcasts. So I did what any good stalker would do. I planted myself about 3 rows behind him and stared and smiled weirdly at him for about 10 minutes. Finally, my excitement got the best of me and I launched myself at Dr. Preston Campbell. He quickly decided I should speak with Dr. Beall. He led me over and introduced me to him. I know that I squealed, covered my face with my hands, and jumped up and down before I threw my arms around him. This is not normal behavior for me. I hugged him hard, thanked him, and I think both Campbell and Beall cried a little bit too. Since people were pouring into the room, we didn't have much time. Somehow, within a span of about 15 minutes, I landed a reserved seat in the FRONT ROW DIRECTLY IN FRONT OF THE SPEAKER! I was seated right next to the Foundation big wigs and major donors. It was amazing and surreal to watch the next few hours unfold. The Plenary Session today was about the progress of the last 25 yrs in CF research. It was like music to my ears. I was lucky enough to meet some families in the CF community including Lindsay Shipp and her mother Barb. Lindsay has participated in the VX-770 trials...and is also an amazing singer/performer. She sang for us at the VIP dinner that I snuck into(thanks to Raven and Britt!). I'm so thankful for people like Lindsay, who have done so much to pave the way. Not to mention that she was just a beautiful little firecracker that lit up the room. The VIP dinner was attended by only 117 of the 4000 attendees, so there were some important people there. I heard that Bob was talking about me at his table, so we decided it would be a good time to give him the book of pictures and letters from all of us. THIS IS WHEN I KISSED HIM! 3 times I think. We took pictures and he was very appreciative. I thought it couldn't get much better until later in the night, right before I left he told me, "In all my years, this is the most thoughtful, nicest gift anyone has ever given me." I just about lost it. For those of you that contributed, please know that he loved it for real. I decided I'd better get out of there so I could cry it out in private. All happy tears. Surreal, overwhelming happy tears. My coffee meeting with Bob was changed to 2:00 tomorrow afternoon and I learned that I will get the opportunity to film a "my dream for CF video" for the Foundation also. The absolute only way that today could have gotten any better is if my shoes were more comfortable. Please excuse any typos or errors. It is very late and I'm exhausted. More tomorrow. Can you feel me smiling?
Saturday, October 22, 2011
Ch-ch-ch-ch-changes
I vowed to share our story through each step of this so here I go. My mind has been in a million places the last few days so I’ll try my best to make this understandable. First, let’s recap: Brady is recovering from his recent endoscopic sinus surgery and seems to be breathing much easier. He is making comments during meals like, “mmmmm, tasty mom” that indicate to me that he is finally smelling and tasting his food. His appetite in general seems to have increased. He is not snoring at night and can breathe through his nose during the day. Awesome. Want to know what is even more awesome???????
NEWS FLASH! Vertex Pharmaceuticals submits new drug application to the FDA on Oct. 19th for VX-770(Kalydeco—Kuh-LYE-duh-koh)! It is strange to see VX-770 with an officially trademarked name associated with it! At first I didn’t like the name. Now, it makes me think that CF is about to collide-aco with my fist. Dumb I know…but it helps me remember the name. It is hard to describe how it feels to actually realize a goal like this. When I learned about VX-770, Brady was an infant and the drug was in Phase 1 trials. The chances of any compound making out of that first phase are so small. Years pass and VX-770 progresses through phases 2 and 3 of clinical trials with incredible results. Today, the FDA considers this drug for marketing approval in the U.S. When it becomes available…everything will change for us. Am I dreaming?
Today I also booked my flight and hotel for the North American Cystic Fibrosis Conference in Anaheim Nov. 3-5th. I went back and forth over whether or not I should attend…it is super expensive. A few weeks ago I decided I should just stay home and watch the webcasts. Then the application went to the FDA and I got the most unnerving feeling in the pit of my stomach. I felt so sick thinking about this conference going on without me so I instant messaged Brock at work, hoping he would agree to take time off work and let me go. I feel like I’ll regret it for the rest of my life if I miss it, so I’m going.
An hour later, I’m registered and my trip is booked. You’d better believe I’m going to share everything I learn. I know there are so many other CF parents out there still waiting. For some reason, Brady has that random genetic mutation that gets to benefit first…I will pay it forward every way I can. I feel so nervous and excited. My son’s entire clinic team is also attending and I’m looking forward to “hanging out” with them in a social setting. I can’t believe I’ll be rubbing elbows with the scientists who developed VX-770, and the President of the CFF, Dr. Bob Beall. They are like celebrities to me and I’ve got butterflies just thinking about it! I will also get to meet a few CF parents that I’ve come to know through Facebook. It is all becoming so real.
There has been a flood of information online in the last few days regarding the Vertex drugs and details of the clinical trials. One man wrote that he had achieved a 99% FEV and had stopped most of his other CF medications after being on VX-770 for a while. This is what I hope for Brady. I hope he can someday stop his crazy shaky vest and constant expensive airway clearance medicines…and just take Kalydeco and enzymes…and be healthy.
My primary goals at the conference are to:
1) Meet and kiss Dr. Beall2) Learn inside information about the trial for 2-5 yr. olds that Vertex is planning for 2012. I need to know details for obvious reasons. My hope is that the trial is set to start at the beginning of 2012! This is the best, easiest, cheapest, most lawyer free way for Brady to get the drug. I’m worried that if we try to obtain it by regular prescription, our insurance company will deny coverage. The drug will be super expensive and has only been tested in children aged 6+. Brady will only be 4 when it is approved so we expect a fight. I need to find out the parameters of the trial. Is it placebo controlled? I want the real drug for sure. Brady’s nurse seems to think that it might be designed more like a rollover study where everyone gets the real drug, because efficacy has already been proven. Also, when exactly do they plan on enrolling and starting the trial for 2-5 yr. olds? The sooner, the better.
3) Meet and thank people from my CF community.
It feels like something big has happened even though nothing has actually changed. We are still just sitting here waiting for the little blue pill. Still, there have been some ch-ch-ch-changes in my mind. The weight of CF has begun to lift and I’m allowing myself to imagine distant futures. It is starting to feel like everything might just be OK, so I can relax for a goddam second. Last night, I slept better than I have in years. It is just such an amazing flood of relief washing over me. The profound impact that the Vertex news has had on me has allowed me to really cruise through Brady’s recent surgeries with a positive attitude. Also, it is tough to be negative when he is so stinking brave about everything. After both surgeries, the anesthesiologist told us that Brady wanted to hold the mask himself while inhaling the medicine to put him out. He was a cool, calm, star patient and they were really impressed by him. He is an unstoppable force. Just imagine if he had a chance at a regular healthy life…oh wait, he does J I am so happy, hopeful, and thankful. Now I just need to figure out what to say to the people responsible for making this happen. How do you thank someone for a gift like that? I have less than 2 weeks to figure it out! So far, all I’ve come up with is blubbering tears.
I’ve been asked by lots of other CF parents to report what I learn at the Conference and I promise detailed updates!
Friday, August 5, 2011
The Big Picture
It has been a tough couple of weeks…but I cannot be distracted from the big picture. Brady had been having a hell of a time breathing and sleeping because of swollen, chronically infected tonsils and adenoids. He had surgery to remove them on July 28th. I know lots of people have had their tonsils removed, but I think it has been a little tougher for Brady. He has to swallow a ton of pills every day, no matter how much his throat hurts. His breathing treatments have definitely been a challenge also. One inhaled treatment is concentrated salt water, and while probably very therapeutic, seems to burn quite a bit. He has been complaining during his vest treatments too. I suppose being shaken like crazy doesn’t do much to soothe raw surgical wounds. I feel so bad. CF just sucks. It makes his life so much harder. And my heart breaks when he sees me coming toward him with another handful of pills and he starts to cry. Or when I am sitting next to him for his treatments and all I hear is a muffled, “mommy my throat hurts” from behind his nebulizer mask. Fortunately, we are now over a week post-surgery and things should start getting a lot better soon. That is worth repeating…Things should start getting a lot better soon.
The day Brady had his surgery; Vertex announced their plans to apply to the FDA with VX-770 in October, 2011. This October. Just a few months away. And while I know there are a million variables that could affect the outcome, VX-770 does have fast-track status with the FDA. Vertex Pharmaceuticals managed to get another one of their new drugs (Incivek for Hepatitis) approved earlier this year in less than 2 months! Vertex was prepared and was able to make Incivek available to patients 3 days after the approval. VX-770 has superstar clinical data with only a few minor adverse side effects reported. Honestly, I think they are in a good position for a hasty approval. I am trying so hard to think about this objectively. I can’t even guess how many scenarios I’ve played out in my head concerning when and how Brady will get his drug. My latest goes something like this(cue dreaming sounding background music)…Vertex submits their new drug application in October and is approved by the end of year. 2012 starts off with a bang and VX-770 drops from the sky with a little silken parachute into my hands. I’m pretty sure the bottle will be encrusted with jewels. I rub the bottle and a genie pops out. He doesn’t even ask what my wish is, he just hands me the little blue pill. At that point, I drop to my knees and give it to Brady(very dramatic, tears streaming down my face). He swallows it and runs off to play, as if nothing ever happened. But for Brock and I, there is a palpable shift in our universe at that very moment(I know, soooo cheesy right? Big deal, it is my fantasy!) Back to reality, I’m so curious to know how I will feel right then. I try to be thankful on a daily basis, but this is new. This is something I would gladly give my life for. It must feel awesome to receive a gift like that. It is something I’ve dreamed about every day since his diagnosis. I have never wanted anything more. Never. And now it is practically here. It is happening. There are still thousands of people with CF that won’t benefit from this right away so it seems like an even more personal miracle. When I first read about Vertex’s research, Brady was an infant. I dreamed up my first scenario that day. As the years passed and further trial results were published, I obviously became more and more obsessed. This couldn’t be better if I had scripted it myself. Why the hell am I so lucky? I have been trying to stay busy and focus on other things for my sanity. Trying is the key word there. My detox diet has been a nice distraction. I want to look my best for all the television interviews I will be doing when Brady is all fixed up and the world wants to marvel at him ;) I hope Brady’s pharmacy will agree to deliver via silken parachute(horse drawn carriage would be a second choice)…just this once!
Wednesday, June 15, 2011
Why I need coffee
It is impossible to look at Brady and imagine what his day is like…but here is what he actually does most days. It is a demanding schedule that is sometimes very difficult to adhere to, for everyone. We are happy that all of Brady’s medicines are in pill form now. He used to have to swallow some disgusting liquid vitamins, and other liquid medicines. Getting the prescription filled is one thing…getting the medicine inside the child is quite another thing. We are lucky that Brady is very compliant with his treatment schedule. As you will see, Brady has to do something CF related every few hours throughout the day. It makes things like traveling and having a social life difficult sometimes, but with planning it can be done. It is a lot of work for Brock and I, so it is a good thing that Brady is so darn cute. I have Disney Pixar movies and white Russian cocktails to thank for getting me through some difficult times. Keep in mind that the schedule below is the “healthy” schedule. If Brady is ill, breathing and vest treatments are added. Let’s just say that I will be smiling from ear to ear as Brady is able to be taken off several of the medicines and treatments in his schedule after VX-770 is in his system for a while! That is our hope and what I truly believe will happen. Anything is possible!
7:00 a.m. Wake up—The first thing I do when Brady wakes up is give him his Prevacid capsule in a spoonful of applesauce. He used to swallow his enzyme beads in applesauce and was used to just gulping it down without chewing, so I started sticking pills in the spoon whole when he turned 2. He stilI swallows his pills this way, which means he eats a ton of applesauce. Fortunately, he loves it. I get him some OJ and spike it with a liquid fiber supplement. He needs a drink nearby for treatments. If I have time, I begin preparing his morning treatments before he wakes up. Basically, I have to wash hands, prepare nebulizers with correct medicines, take Brady to potty and get him in his vest, and get something sweet on the TV to occupy the next 45 minutes of our time. Brady inhales his Albuterol (about 6 minutes) and then his Hyptertonic Saline solution (about 18 minutes), and then we turn on his Vest to shake the crap out of his lungs for 20 more minutes.
8:00 a.m. Breakfast. While he is finishing his vest, I begin cooking his breakfast and sterilizing his nebulizers. After every single session, his equipment gets cleaned. First, wash nebulizers in warm soapy water and rinse. Next, sterilize them in an electric baby bottle steam sterilizer. Finally, air dry them in a little device called a “Germ Guardian” that uses dry heat to kill germs. Boring. Moving on… I cook something special for him every morning. I strive for a minimum of 15 grams of fat and 15 grams of protein at meals. He is usually pretty hungry and goes to town on Pediasure and eggs scrambled in tablespoons of butter. His other breakfast faves include: frozen fortified whole grain waffles soaked in butter and pure maple syrup, rice with raisins, cinnamon, and ½ n ½, and double fiber toast with PB, honey, and butter. At breakfast, Brady takes 5 ½ more pills: 3 Zenpep, 1 Ursodiol, ½ Source CF chewable vitamin tablet, 1 Singulair pill. All this crap takes a while. The time is extended by the fact that Brady is the slowest chewer in the universe.
9:00 a.m. Party time. Put on sunscreen and go to the park, library, etc… I usually try to eat some breakfast and wash my face around this time. Brady is occasionally kind of pissed that I’ve been making so many demands of him and wants to do something fun. If the weather is permitting, we go outside. He needs exercise every day for his lungs and this is usually the best time to get it.
12:00 p.m. Lunch time. Brady’s favorite lunches right now are: elk burgers and chips, or creamy cheesy pasta with bacon sprinkles and a side of black olives. Can’t say I blame him. He takes 5 ½ more pills at lunch: 3 Zenpep, a fish oil pill, an antioxidant Juiceplus capsule, and ½ a chewable vitamin(I break his vitamin in 2 because it is super strong and has a tendency to hurt Brady’s stomach and make him puke). I always offer him Pediasure or Boost at mealtime. He doesn’t need enzymes to process juice, so I mix juice with water and give that to him between meals.
1:45 p.m. Nap time. Brady usually sleeps between 2-3:30 or so. He loves his nap and I am pretty strict about it. I feel the extra rest helps to keep his immune system humming.
4:30 p.m. Dinner time. Prepare meal and give 6 more pills: 3 Zenpep, 1 fishoil, N-acetylcysteine capsule, and Juiceplus antioxidant capsule.
6:30 p.m. Breathing treatment time again. In the evening, he does the same as in the morning, plus one additional breathing treatment (Pulmozyme—takes about 6 extra minutes). It takes an about an hour to do it all. Usually Brock does his evening treatments with himJ There are 2 nebulizers to sterilize again just like the routine described earlier. *Brady spends about 1 hr. 45 min total every day doing treatments for his lungs. I bet we spend 20 min sterilizing equipment every day plus time to set up and put away all the machines.
8:00 p.m. Night time snack plus 6 more pills:3 Zenpep, calcium pill, antioxidant Juiceplus, Ursodiol. We have to try to cram a few more calories in before bed. Hopefully they go straight to his tiny butt! Buttered graham crackers, buttered salty popcorn, and vanilla milkshakes are favorites for this snack. We can never let up on the calories or his weight gain completely stalls out or he starts losing! It is a huge source of stress for me.
8:30 p.m. Shower. We try to bathe or shower Brady every evening to keep allergens and bacteria off his skin. It is pretty annoying right now because he fights it. If we don’t do it, his nose gets all stuffed up and he snorts and snores all night. Boo allergies!
Medicine Guide
This is just a brief description of the medicines he takes. (Brady takes an average of 23 pills a day, That works out to 690 a month. 8280 in a year.) Prescription drug coverage is of supreme importance for us! Brady’s medicines retail approximately $4500/mo.
Prevacid—Acid blocker. Assists action of enzymes.
Zenpep—These are the digestive enzyme pills that Brady must take with everything he eats. He generally takes 3 at each meal, but the dosage gets adjusted based on what and how much he is eating (which is sometimes anybody’s guess!).
Ursodiol—This pill assists his liver function.
Singlulair—Asthma pill
Fish Oil Supplement—helps body with inflammation, which is a concern in the lungs in CFers
JuicePlus Antioxidant Supplements—These are a whole food supplement made with a variety of fruits and veggies. There are 3 different pills: fruits, veggies, and berries. That is why he takes 3 of them each day. Brady is a very picky eater and I feel like this is at least something I can do to help fill the gaps in his diet. I was skeptical, but there has been a decent amount of clinical research regarding the effectiveness of raising antioxidant levels in the blood when using this product.
N-acetylcysteine—powerful antioxidant. The body uses NAC to synthesize glutathione. I try to get Brady to take the effervescent kind from Bioadvantex, but he doesn’t like the taste right now so we are doing caps for a while. NAC is a readily oxidized compound and pills often lose a lot of their potency by the time they are ingested.
Albuterol—bronchodilator. This medicine is used by a lot of people with asthma because it opens the airways. Doing this medicine first allows all his other medicines to get deeper into his lungs.
Hypertonic Saline—This is a 7% salt water solution (about twice as salty as seawater). Depositing salt on the inside of the lungs draws water to the lung surface. Hydrating lung mucus allows Brady to get a couple of good juicy coughs out and move some of that junk loose. I’ve heard from adults that this is very irritating to inhale. Sort of like sandpaper. Brady doesn’t seem to mind.
Pulmozyme—This is a super expensive inhaled breathing treatment that breaks up mucus in the lungs.
Saturday, May 14, 2011
thick skinned
When I was just beginning my chemistry studies in 1996, scientists were stumbling upon the first Vertex compounds VX-770 and VX-809 in a lab. A series of events and investments followed those discoveries to bring us to where we stand today...at the door of the FDA with a groundbreaking new treatment not only for CF, but for all genetic diseases. The fact that Brady is part of the tiny population(1200-1500 people is what I have heard) that will be able to benefit from this drug right away, is something that I give thanks for every day. It is not lost upon me for a single second that when VX-770 arrives to help Brady, thousands of others with CF will still be suffering. Bittersweet. I would be lying if I claimed that I wasn't so involved in supporting the CFF for completely personal reasons. I NEED my baby to be alive. At the same time, I feel a connection to this community that is more powerful and compelling than anything I've ever experienced. I love several of the people, especially other moms, that I have met through facebook etc... that make me feel like I am not alone. For those of us that live with CF every day, I don't need to explain to you how much the support from friends, family, and community at Great Strides time means. People frequently tell me that I seem "dedicated" to supporting the CFF. My response is always, "there is a fine line between dedication and desperation."
I am really just a mother, who is not about to stand idly by while their child is destroyed. I remember the day I learned that Brady had CF as the worst day of my life...but it is also the day that things came into focus. Absolutely nothing has changed my personality or outlook on life the way dealing with CF has. Before CF I based my life on "plans." The life I have today is certainly not the one I had planned, but I feel more focused and determined than I ever have before. At this point, I see life as the wildest ride I could ever imagine and I am just trying to hold on. When I decided that fundraising for the CFF would become my mission, I basically committed to sharing the journey with everyone in my path. People don't want to donate to a disease that they know nothing about. Be warned that sharing your CF story can be a painful road that will leave you vulnerable, wounded, and frequently sobbing in your car. You have to place your battered heart out there constantly and hope that the reaction you get doesn't just finish you off. I can't begin to explain how important it is to me that people stand up and get behind me when I do an event like the "2nd Annual On Par for a Cure Golf Scramble," or the Great Strides Walk. The money contributed to the CFF is going directly to the research that is controlling CF. That research could be drastically changing our lives within the next year. How much closer to the action can I get? I must remain focused. For me, fundraising is one of the only things that feels really good, like I'm doing something to help. I would be lying if I said that I don't take it personally if my friends and family support the CFF. If you aren't interested in helping me keep my child alive, well, I'm not sure we have much to talk about. Is that fair? No. That is sort of like saddling the rest of the people that love me and Brady with CF too. But is it fair to try to pretend like I don't mind if people who claim to be my friends are suddenly too busy and broke at Great Strides time to contribute? Hell no. The people that attend Great Strides are more important to me than those who attended my wedding. I don't know how else to put it.
I feel an enormous responsibility to repay the work that the CF Foundation has already done and make sure that everyone suffering from CF gets to benefit from a genetic modifier like VX-770. It is emotionally draining to be so angry at CF and so ecstatic about VX-770 at the same time. I know a local man who underwent a double lung transplant a week ago because of his CF. He very nearly died. The clock never stops ticking when CF is in your life. Every day I tell myself that once Brady has his new medicine, I will have so much more time and energy to devote to fundraising. It is a surreal feeling to know his medicine is coming so soon. I feel "guilty" being one of the first CF moms to be staring this breakthrough in the face. Why are we so lucky? We haven't paid our dues the way so many other families have. God, I will try to pay it back. I will never stop fighting. As much as I hate it, I will keep approaching everyone I know (and don't know) to ask for help to cure CF. I absolutely despise asking for money and sometimes I swear I would curl up and die if the person I beared my soul to decided to reject me.
So thank you friends. Thank you family. Thank you dozens of businesses that donated to my golf tournament. Thank you stranger who decides to volunteer. Because of you, I won't go completely crazy today. Because of you I will put my old beat up heart out there again tomorrow. and thank you also to the mean lady that yelled at me for asking for her help. Because of you, my skin is thicker and I will try to never allow "no" to get me down. What an extraordinarily lucky life I live. Who knew that giving your heart an absolute beating could be so rewarding at the same time?
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