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 ;-)

The boys from the NYPD choir were singing Galway Bay...

It could only be this really, couldn't it? Best Christmas song of all time?

Happy Christmas to all and to all a good night!

Christmas Countdown: Maybe this Christmas

Just heard this recenty on Radio 2. A beautiful song. Most famously used (I think) in montages on The OC and Gossip Girl. Joe should have covered this for his X-Factor single; he probably would have got a number one instead of Rage Against The Machine, although I shudder to think what Simon Cowell would have done to the song (Key Change, Choir, etc) ;-)

Christmas Countdown: 2000 miles

I love Chrissie Hynde's voice, it's so warm and soothing, like a glass of mulled wine at Christmas...

Countdown to Christmas: Donner and Blitzen

I'm going to post some of my favourite Christmas songs in the build up to Christmas! Starting with this from Manchester's own Badly Drawn Boy:

Snow and the last outpatients

Went to the hossy last week. It was mainly for a checkup with the phsio about how I had gone on with the Tobi trial last month. To my grumpy annoyance the blows were the same (FEV1 2.85 / 3.8) but she said that was a good thing; the important thing in the first month of the Toni test is to make sure that the volume does not fall, as that would indicate some kind of allergic reaction (to the Tobi) was going on. She did notice I had a wheeze at the end of the spirometry blow, so we discussed me going back on Uniphyllin to help combat it. So anyway the plan is next month to ditch the crappy old Pari Neb and start on the Tobi trial through the iNeb next month. (on a one month on, one month off basis) By then the outpatients will have moved from the Heart area to the new outpatients above the new super Pearce ward. (where it is alleged you can watch Sky Sports and get foot massages...I should be so lucky ;-))
I've also got the notes back from the doctors telling me what my Genotype is: G551D/N1303K.

Other news, Oscar has been really poorly for the last week with a D&V tummy bug, which promptly spread to R, her in-laws, and finally, me, despite washing my hands continuously and rubbing with alchogel afterwards (I now have the hands of a 100 year old man!). Being ill I've not really eaten for 4 days and I feel like that skinny guy out of Twilight (only not as tall)

Anyway, on Sunday it properly snowed in Stockport for the first time in years, so we took Abbby sledging down the golf club, and she loved it. Later on though we nearly got snowed in at the in-laws house when the roads froze and all the cars going through the village couldn't get up the hill to get out. For a while it was like vehicle civilisation had ended and we were back to doing everything on foot! Me and R were serious about settling the kids down at the in-laws and doing a 6 mile snow hike back home in the dark to get supplies and then walk back in the morning, but by the time we went back down to the village, the temperature had risen slightly and the snow was beginning to melt. I was slightly disappointed, but only slightly, because my legs were already beginning to stiffen up after walking for 20 minutes in the snow, so god knows what they would have been like after 2 hours plus. Would have been romantic though, it's great to be outside at night in the snow, everything is so quiet because the snow absorbes all the sounds, and covers all the hard edges, I just love it.

Anyway, everyone seems to be on the mend, so bring on Christmas!

Oscar's imaginary CF!

I really don't think our (18 month old) Oscar has got CF, btw, but some of the similarities are a bit disconcerting:

• Chest infections. Oscar was on ventolin and (banana flavoured) Amoxicillin after a virus he picked up last week moved onto his chest and gave him a chest infection. By yesterday his breathing was really-really wheezy, laboured and clicky, you could tell there was loads of gunk down there, and he just wasn't himself, he would play for a minute or two, but then he would roll around on the floor screaming until he was picked up. (carrying a 21 pound toddler around all day is a bit of a strain on the back!) I phoned the emergency doctors and the nurse on the phone who filters the calls before giving you an emergency appointment was a real bitch; I tried to explain to her what the situation was but she kept interrupting and cross examining me like I was in court or something, I felt like saying "look I have CF and I know what a chest infection sounds like, if my chest was as bad as Oscars I would be checking myself into hospital for some IVs!" Anyway, we eventually got referred to a doctor who agreed he had the startings of a chest infection, we then had to dash across town to get to a 24 hour pharmacy in Fallowfield. We then gave him the ventolin and amoxicillin (with a baby spacer to breath the ventolin in with) and in the morning he seemed to be a lot better.
• Constipation / blockages. Oscar was on lactulose for being blocked up, but then he seemed to get things under control. Then after another week or two he went and got really blocked again so he was put on Movicol, twice a day, decreasing to once a day when his bowels settled down.
  

Here's some pictures of me and Oscar clowning around in the supermarket on the day he had his chest infection. He was fine in the morning while we were shopping then he went downhill really fast in the afternoon. Then he was much better in the morning. Kids eh?