Miracle Drug

It has only been 4 days. 4 days.

Wow. As the saying goes I'm only 4 days in but I already feel loads better. Mucus is still coming out, but it's coming out easier and it doesn't overwhelm and exhaust like it used to. My bowels feel normal. They haven't been normal since I was 22. My blood sugars seem better; normally I get a crashing feeling of dropping energy levels if I leave big gaps (i.e. 2 hours) between meals. Haven't had that yet.

On Friday I went for a run at the gym and stuff was flying out of me so much that I had to keep pausing the running machine every few minutes to run to the toilet and bring up more mucus, it was gross but good! Easier to bring up. Did I have more energy in my legs for running? Or was it in my head?

In the morning I'm not overwhelmed by mucus in the back of the throat; I can talk to my misses first thing in the morning without worrying about having a coughing fit!

I went for night out with some friends in Manchester to celebrate the arrival of K (on Saturday) It was an epic night out where we tried to pretend we were 18 again and we all had a lot to drink (like you have to do, once in a while ;-)) This normally gives me a really bad CF hangover with low energy, really bad bowels, and double the mucus for the entire day (sometimes 2 days). There was hardly any mucus first thing in the morning! There was a bit more through the day but nothing major, I didn't even feel tired!

For the last four years I have been in a gradual decline, I think the running (have entered the Manchester 10K for the last four years for the CF Trust) and mountain biking has hidden that decline a bit, but after taking K for 4 days I have realised just how bad that decline has been. I couldn't talk for mucus first thing on the morning. The decline has now been taken away and I feel 5 years younger.

I am in awe. I keep tearing up. There aren't really words.

Victory for Kalydeco!

Ok sooooo....tomorrow I will be receiving my first dose of Kalydeco / Ivacaftor / VX-770. Last week (Monday) I had my baseline tests done (loads of blood tests and my first sweat test since I was diagnosed back in 1981 when I was about 9 years old.) My sweat test was around about 109 so we will see what happens after I have been taking it a few months. It has been shown to consistently reduce PWCFs sweat tests to below the CF diagnosis line (60). Baseline blows were irritatingly high considering I need to prove to the SCG that I am benefiting from K after six months. FEV1 was 2.6, FVC was about 3.4 I think. FEV1 was the highest it's been in 8 months, I'm going to assume that is down to the nebbed Cayston, which I have been having my first dose of for the last 10 days - The docs have told me to stop that now so they can measure the benefit of the K on it's own for the first month or two.

I've been following this drug since 2009 when I first tried to get on the trial; and although it was all very promising (I tried to enrol in the trail but was a few weeks too late due to my genes being lost in my notes, grrr) I think the penny finally dropped when I read this article:

http://commonhealth.wbur.org/2011/05/cystic-fibrosis

It was this bit which amazed me, the first Eureka moment for CF R&D?

"At first, she thought maybe she was just having a good week, or month. Then, she started to bring up more mucus. “Actually, it felt like a flash flood,” she said. “I would cough and it would just come flying out of me, not to be too gross. It was just everywhere. It was much thicker than it used to be. It was constant, all day long, and I thought, ‘Oh, crap, I’m getting sick,’ but I never actually got sick.”

“And as time went on, my amount of mucus decreased, and my cough decreased. Then I started noticing bigger and bigger changes. I was sleeping. I was able to maintain my blood sugars. I could basically eat and not have to worry. I no longer needed any medication for constipation. And the biggest thing for me was, that year was the first year in my entire life that I never got sick.”

"Roe has a port in her chest for intravenous antibiotics. She hasn’t used it since she started the trial in 2009. And more: before she started on the trial, she had a “huge mucus plug” in her chest so bad that she was considering surgery to remove part of her lung; now it appears to be gone.

As she spoke to the Children’s Hospital cystic fibrosis team, she mentioned that her FEV, a measure of her lung function, had been 62%. Now it’s 81%."

The first months supply for me arrives tomorrow. We shall see...:-)

End of ABs and the real work begins

Sorry for this geek post ;-) Last week it was the end of oral antibiotics and my lungs felt better without feeling *deep down clean* the way they do with IVs, however if you compare these two races - then my all round fitness does seem to have improved since the start of the minging infection (March 8th was in the middle of the infection and I was coughing all through the ride, March 22nd is on a sunny day today 1 week after the ABs) so hopefully I'm on the road to recovery...

Back to Activities

Bramhall Loop Road Cycling Tue, Mar 22, 2011 12:09 PM

Bramhall Loop Road Cycling Tue, Mar 8, 2011 12:38 PM

Summary

Distance	7.52 km	7.21 km
Time	00:29:28	00:33:02
Avg Pace	03:55 min/km	04:34 min/km
Calories	225 C	310 C

Avg HR (bpm)	123 bpm	131 bpm
Max HR (bpm)	148 bpm	151 bpm
Avg HR (% of Max)	66 % of Max	71 % of Max

http://connect.garmin.com/activity/comparison?activityId=74473657&activityId2=71944384

Last week I visited the hospital outpatients and was seen by Proff Web, it was nice to have a catch up with the grand old duke of CF ;-) because I rarely see him in clinic these days (he's semi-retired I think, but certainly knows his stuff). In the end we didn't talk about the usual CF things like I would at a normal oupatients clinic, we just talked about the good old days when I first moved to the Adult CF Hospital and the progress of the VX-770 trial. I was a bit depressed about the potential cost of the drug, and whether NICE would be able to fund it, but I talked it out on the forum and now I feel a bit better about it. FEV was 2.65 and 3.2 which is a bit down; I'm hoping it's going to pick up as I pick up the exercise...

Gene Therapy Trials

Been thinking a lot about Jess today, and the truth is, I can't really comprehend what CF is like for someone like Jess because CF is a completely different beast for me; it doesn't really impact on me that much. Sure, I take the same tablets, nebulisers, IVs, and do a small amount of physio and exercise... but CF doesn't really restrict me in the way that it does someone like Jess. While I was getting drunk, popping god knows what, and generally having a carefree time at university, Jess was on the transplant list and her life was very much on hold. It's taken me a long time to actually connect with the CF community, I think a lot of this is down to fear of what happens to others happening to me, I've been dimly aware of the more severe aspects of CF though my two stays in hospital when I was in my twenties; I met other people with CF who were having a much worse time of it than me and to be honest it scared the hell out of me; maybe because of that I never really looked at it in focus, I always kind of kept it at arms length. It's only in the last couple of years that I've begun to find some kind of acceptance and begun to seek more knowledge about CF and what it is, and how it affects others as well as myself. And what have I discovered? Well, it's tough, and the people that have CF are bloody tough. And an inspiration. RIP Jess, you are braver than I will ever be.

On a more positive note -because hopefully Gene Therapy can one day prevent the severe lung damage like what Jess has suffered- this VX-770 trial that I've just missed out on has opened up something of a rabbit hole for me which is going to take a while for me to sift through and figure out. I've just had a quick scoot around to see what's happening with gene therapy trials. I still don't understand how the CFTR works, but when I do I'll let you know...

VX-770
VX-770 is a drug being tested by Vertex Pharmaceuticals in people with cystic fibrosis who have at least one copy of the G551D mutation. The drug may actually be able to target the defect in the CFTR gene and restore its ability to open up chloride channels, thus allowing salt to flow in and out of the cells properly. Unlike gene therapy, VX-770 would not replace the defective gene. Rather, if successful, VX-770 would repair the problem in the existing gene. Patients who took the drug showed significant improvement in several key CF measures, including lung function, nasal potential difference measurements, and sweat chloride levels. The findings suggest that VX-770 improves function of the faulty CFTR protein. This is the first time that any potential therapy has improved the abnormal sweat chloride (salt) levels in a person with CF. Excessive sweat chloride is a key clinical indicator of cystic fibrosis.

VX-809
VX-809 is another drug being tested by Vertex Pharmaceuticals in people who have two copies of the ∆F508-CFTR mutation. It is similar to VX-770 in that it may be able to get salt flowing through the cells properly, but it works a little differently. If it works as researchers hope it will, VX-809 would open chloride channels by moving the CFTR protein to its proper place on the airway cell membrane.

Miglustat
Miglustat is a drug manufactured by Actelion Pharmaceuticals that is already in use to treat other conditions, but it is currently being studied for use in people with cystic fibrosis who have two copies of the ∆F508-CFTR mutation. The study is small scale -- consisting of only 15 participants -- but so far the results have been promising as Migulstat has been able to reverse the CFTR defect and restore normal activity to cells.

Ataluren
Ataluren, which was once called PTC124, is being studied by PTC Therapeutics as a possible cure for people with CF who have nonsense mutations. In nonsense mutations, a piece of “gibberish” code appears amidst the normal code in the CFTR gene. The nonsense code acts like a stop sign, preventing the cells from reading any code that occurs after it. Ataluren may be able to correct that problem by helping the cells to ignore the stop sign and keep reading the code that occurs after it, thus restoring normal function to the cells.

http://cysticfibrosis.about.com/od/cysticfibrosis101/f/cure.htm

Doh!

Just missed out on the VX-770 trial. I asked my CF Team what my genotype was in September. Unfortunately it was buried in my notes somewhere so the team had to get a third party Gopher to find it from my notes. I got the letter back on Christmas Eve, probably missed out on the trial by a matter of days. C'est la vie...

From: J
Sent: 11 January 2010 15:00
To: DJC
Subject: VX-770 Trial

Hello ,

I am a 38 year old male with cystic fibrosis. I have recently learned that my CF Genotype’s are G551D / N1303K. I have been told that I may be eligible for the VX-770 medical trial. Would it be possible for you to give me any further details?

Kind Regards, J


From: DJC
Sent: 11 January 2010 17:22
To: J
Subject: RE: VX-770 Trial

Dear J

I am really sorry to disappoint you, but recruitment to the trial you mention closed just before Christmas as the drug company had exceded the numbers they needed.

On a brighter note, they are planning an interim analysis after everyone has completed 6 months of treatment, ie. early summer, and if things are looking good, they will be applying for a license to allow your clinical team to prescribe this agent. It's difficult to predict how long this will all take, but they will certainly be trying to get it through as fast as they can.

I'm sorry not to have more positive news for you personally

Best wishes, J

I'm not too disappointed by this really; in the long term this is good for the CF Community because we are actually getting to the stage where we may be able to take a gene-correcting drug that may stop things like pseudomonas getting established in our lungs, it may stop our pancreases becoming progressively more damaged, and it may prevent us developing diabetes. Fingers crossed!

Further reading here on the cystic fibrosis transmembrane conductance regulator (CFTR), and on G551D and N1303K. If anyone can explain to me in more detail how the CFTR works then please let me know ;-)