4, 8, 15, 16, 23, 42...

The final season of Lost is just around the corner. I'm so excited! Well almost...I must be the only person still watching this! Hopefully this time we'll get some real answers as to what the hell's going on as well ;-)

Questions:

• Who is Locke?
• Who is Jacob?
• Who is Richard Alpert and why does he never age?
• What is the black smoke?
• What happened to Claire?
• Why is Jack's dead father on the Island and is he really dead?
• Why spend 4 seasons trying to get off the island and then spend the fifth season getting back on?
• Could the people in the past (70s!) change the future or has it already happened?
• Does free will exist?
• If I can't exercise my free will not to watch the final season does that prove free will doesn't exist?
• Is Juliet hotter than Kate?

Last night I went for my first jog of the year. Just went for a run around the estate for 10 minutes after R had done her run. Didn't feel too bad, although the cold night air made my lungs burn. I made sure I took my seretide, ventolin, uniphyllin so that my lungs didn't seize up. Oscar has come down with yet another cold, he's not really full of it in his nose and throat, he's quite hot and he doesn't seem quite himself.

Last of the snow in pictures

Some pics of going sledging in the snow last week before it all melted. We went to see some friends up in Ramsbottom (in the hills) in North Manchester and it was freezing cold ;-)

2009: Stop me if you've heard this one before...

Bluffin' with her muffin? You'd have to have been deep in the amazon jungle to have escaped this song, it was everywhere in 2009. The greatest pop song of 2009? Up for debate obviously.

The thing with Lady Gaga now is that it is becoming impossible to talk about her songs without talking about her image in the media, and she undoubtedly makes good copy and sells plenty of papers. She probably can talk art/fashion bollocks, she can talk about Bowie, Madonna, Warhol and pop-art till the cows come home. Is she faking? Is it all a mask? Who cares? IMHO None of that really matters. All that matters is writing catchy pop tunes that people like to buy and maybe listen to with the volume turned up before they go out on a Friday night. And you can't really fake that.

p.s. I'm a 38 year old dad, surely I'm too old to like Lady Gaga? I'm going to be such an embarrassing dad ;-)

2009: Best songs last year, part 1...

Well, as usual it's taken me a while to get around to listening to Florence and the Machine; but I like this album; there's some great tracks and there are signs she could go on to greater things. I like the way she fuses parts of dance and indie rock. She's definitely one of the more interesting female artists around at the moment. She's not my favourite female artist though, PJ Harvey is still in the lead in that race, with Goldfrapp coming up fast on the outside...now, if only I could get Abby into her, or Lady Gaga for that matter (I bought Abby Lady Gaga's album for Christmas but she was totally unimpressed, she prefers Disney musicals ;))

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 ;-)