The Beginning of the End?

Welcome back!

It’s been a weird day.  I had planned to write about meditation and why having a “lung disease” doesn’t mean you can’t meditate.  This was something I used to actually believe, since beginning meditators are often instructed to “follow the breath.”  I tried this…I really did!  It only made me completely anxious and sure that I was suffocating!

I was going to wax prolific on how it is actually easy to use other objects to “anchor” the mind, and how wonderful it is to start each day with a relaxing (usually) and centering meditation practice, without even thinking about the breath.

Then, as I always (sadly) do before I started to write, I checked my email.  There I saw the following press release , and I literally lost my breath.

Vertex Announces Results from Phase 2a Trial of VX-809 Targeting the Defective Protein
Responsible for Cystic Fibrosis
-VX-809 was well-tolerated at all dose levels when dosed once daily for 28 days-
-Statistically significant changes observed in measurement of sweat chloride suggest increased CFTR
activity-
-Data support planned combination trial of VX-809 and VX-770 in second half of 2010 for CF patients with
the F508del mutation-
CAMBRIDGE, Mass., Feb 03, 2010 (BUSINESS WIRE) — Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced results from a preliminary analysis of data from a 28-day Phase 2a clinical trial of VX-809 in patients with cystic
fibrosis (CF) who are homozygous for the F508del mutation. VX-809, an oral investigational Cystic Fibrosis Transmembrane
Conductance Regulator protein (CFTR) corrector, was well-tolerated across all four dose groups studied. In the trial, VX-809
showed a statistically significant decline in sweat chloride at both the 100 mg and 200 mg once-daily doses, suggesting that the
activity of the CFTR protein was increased in patients during dosing. Additionally, VX-809 demonstrated a dose response in
change in sweat chloride across the four dose groups. On the basis of these results, Vertex plans to initiate a combination trial
of VX-809 and VX-770, an investigational CFTR potentiator, in the second half of 2010. VX-809 and VX-770 were developed
with support from Cystic Fibrosis Foundation Therapeutics, Inc., the nonprofit affiliate of the Cystic Fibrosis Foundation.
“This Phase 2a trial evaluated the potential effect of an oral compound to improve trafficking of the defective CFTR protein,
and its results represent an encouraging step forward in the development of new therapies to treat the underlying cause of CF
in patients with the most common CFTR mutation, known as F508del,” said J.P. Clancy, M.D., Director of the Pediatric
Pulmonary Center at the University of Alabama at Birmingham and Principal Investigator for the VX-809 Phase 2a trial. “In the
trial, VX-809 was well-tolerated across the dose groups, and statistically significant changes in sweat chloride, an important
biomarker of CFTR activity, were observed at certain dose levels. There is high interest in the CF community in new
approaches to CF therapy, and we look forward to the future exploration of VX-809 and VX-770 as part of a novel combination
regimen aimed at treating the majority of CF patients.”

IT WORKS!

Ok, first if you need a review of what this all means, read an earlier post here.  The big news here is that Vertex 809 somehow “corrects” the trafficking problem of the dF508 defective protein…at least enough to cause a change in sweat chloride concentration.  This is huge! We know that another Vertex drug, Vx 770, potentiates  (enhances) the effectiveness of the chloride channels present at the apical membrane in the G551D mutation, and is now being tested on people with the dF508 (most common) mutations as we speak (read, write, whatever we are doing).  So, if Vx 809 gets the protein up there, and Vx 770 opens it….

Is this the beginning of the end of CF as we know it?

Sick and Happy Takes on New Meaning

I am going to be the first ever to blog about the negative effects of happiness in CF.  The following is an excerpt from an article from Stanford Medicine, published yesterday (the emphasis is mine).  In brief, the article reports the discovery of an exaggerated white blood cell response to inflammatory signals leading to lung destruction in CF lungs:

So what are the live neutrophils doing in patients’ lungs? The new findings surprised Tirouvanziam’s team. After collecting fresh neutrophils from cystic fibrosis patients’ sputum and analyzing them with fluorescence-activated cell sorting, the team discovered that signals from the patients’ lung tissue were reprogramming live neutrophils with conflicting messages. The first set of signals switches on what Tirouvanziam calls “an ancient happiness pathway” — a chain of commands that tell the neutrophils that nutrients are plentiful, and that it’s a good time to translate the cell’s library of genes into new protein. The second pathway is a cellular alarm system associated with inflammation and stress.

“They’re receiving a lot of signals at same time, and we think the happiness signals are messing them up completely,” Tirouvanziam said.

His team now suspects the inappropriate activation of the “happiness signal” — the molecular target of rapamycin, or mTOR, cell signaling pathway — may trigger neutrophils to release large quantities of human neutrophil elastase, the enzyme that destroys the elastic fiber of lung tissue. In healthy individuals, neutrophils never release destructive human neutrophil elastase into nearby tissue.

So maybe Sick and Happy should now be called Sick because I’m Too Happy????

Living a Medical Miracle: CF Today and Tomorrow

I thought it would be appropriate to launch my new blog the day I returned home from probably the most exciting CF conference I have attended.  While many of you may have read some of my articles on wellness and exercise before, the purpose of this blog is somewhat more selfish…it gives me something to do while inhaling hypertonic saline.  In fact, I almost called it “The Saline Chronicles,” but I wasn’t sure how to to search engine optimization with such a domain name.  ”Sick and Happy” is more appropriate, because my goal with all this writing is 1) to create help, both with words and with audio and visual assistance, for PWCF to begin and maintain lifestyle practices which will improve quality of life  (after all, isn’t that what we are here for?), and 2) wax prolific on my new favorite subject: how to use the rapidly growing and amazingly popular field of positive psychology to live better in our bodies, such as they are.

Tiffany Christensen, author of “Sick Girl Speaks!” gave an amazing presentation at the start of this weekend’s conference in Redwood City, California.  As she chronicled in a deeply moving and occasionally hilarious one woman show, having CF can be an incredible tool to use when “finding the permanent me.”  Tiffany embodies positive psychology.  It is people like her that I want to learn from, and write about in these posts.  

But before I do that, I first want to describe why this conference was exciting. The bottom line is that there are some amazing new drugs making their way through clinical trials right now. The two I am most intrigued by come from Vertex Pharmaceuticals, and are showing incredible promise.  I never really have believed that there would be definitive treatment for CF in my lifetime, but now I really am starting to wonder.

This makes it even MORE important to do everything in our power now to keep as healthy as we can, using as many techniques as we can.  This blog is another channel through which I hope to communicate  that your future is more in your control than you may think! As my former Pathology mentor, Klaus Bensch used to say, “A scar is a scar is a scar!”  He was of course not referring to CF lungs, but a general principle throughout the body.  It is impossible to revert scar tissue to functional lung tissue.  Therefore, it is even more essential now than ever before to do everything you can to slow down the inflammation↔tissue damage↔infection cycle now.  When a treatment that corrects the basic defect arrives, the more functional lung tissue that you have, the better off you will be for the rest of your life.

So I intend, through this blog, to  use my background as a person with CF, as a physician who understands the pathophysiology of CF more than I probably should, as a fitness fanatic and personal trainer, as an executive wellness coach, and, mostly, as an “old survivor” at almost 48 years old to talk about how to keep on top of your game until that great day comes when you’ll take a pill to move your CFTR to the cell membrane, and another pill to make it work better!

To learn more about me and my coaching services, check out www.newdaywellness.org.  Until tomorrow, smile, a New Day is coming!