RE: Re: Mutations/new on the list

[Guest guest]

Salva,

Thank you for your contribution. This is great information you have given

us. I wish for your daughter that their are no side affects with the

medication.

Tina W., mother of Steph, 18yo wcf

Re: Mutations/new on the list

Hello all from Spain.

After lurking some time and learning so much from this list (not writing

because is difficult for me in English and I had not any important things to

say), I will try to contribute in some questions.

I am the father of a 12 yo girl, Olaia, with cf, and a 15 yo boy, Alvaro,

without. Olaia is doing great till now. She has deltaF508 and g542x.

From what I understand Torin has three mutations: a CFTR gen with two

mutations in one chromosome and one in the other. They don't know witch two

are together and witch alone. That is why they want to study their parents.

One of his mutations is y913x, a stop mutation. That means that gentamicin

could correct the genetic defect. Olaia is on inhaled gentamicin since eight

months ago (in some Spanish hospitals the protocol includes long term

inhaled-gentamicine to prevent pseudomonas colonization). Well I can say

that from the first moment we clearly noticed how the lungs were working

better (much less coughing, and now eight months without a cold). The

problem of the gentamicine are the side effects (possible kidney damage). It

is known that when inhaled the side effects are much lower, but nobody knows

the effect of genta when given during years. For the moment we follow on.

There are some ongoing studies (Cleveland and Jerusalem) about genta, and

looking for any substance with the same effects on

the gene than gentamicin but less side effects.

Salva

[Guest guest]

Hello Salva,

I know currently, there is a pill about to start

human trials, that have the same benefits that

gentamycin has (lets cells produce normal cftr in

those with stop mutations), without the serious

side effects of gentamycin. This is really huge news

for us, for your daughter and anyone with cf where

at least one of the mutations is a stop mutation.

Unfortunately, this is only the case in 10% of the

cf population. Gentamycin could not be considered

an ongoing treatment because of its long term

toxicity, as you pointed out, but this pill (article

included below) could be a major treatment option

for many with cf.

BTW - both mutations my twins have are stop mutations,

so we are really holding our breath that this pill

proves effective without any long term side-effects.

Keep the faith! Good things are coming.

C

Mommy to Mick and Alli, 3 yo twins wcf

---------------------------------------------------

Popping a pill could fix gene defect

11:03 17 October 03

Exclusive from New Scientist Print Edition. Subscribe

and get 4 free issues.

Simply popping a pill might be enough to overcome the

type of genetic defect responsible for many cases of

cystic fibrosis, muscular dystrophy and haemophilia.

An experimental drug called PTC124 produces a working

protein even though the gene remains defective.

Unlike gene therapy, it would work only for people

with a particular kind of mutation. But while gene

therapists are still struggling to develop safe and

effective ways of correcting genetic faults,

treatments like this could be available much sooner.

As many as a third of genetic diseases are caused by a

premature stop mutation - a mutation in the middle of

a gene's sequence that stops the protein-making

machinery at that spot. PTC124 binds to a key

component of this machinery, allowing it to read past

the misplaced stop signal. As a result, the full

protein is made. Normal genes should not be affected,

because their stop codon is at the end of the

messenger RNA strand rather in the middle.

In 1996 scientists showed for the first time that an

old antibiotic called gentamicin suppressed these

misplaced stop signals in human DNA. Last week, the

results of the first randomised, placebo-controlled

trial were published in The New England Journal of

Medicine (vol 349, p 1433), showing that when

gentamicin is applied to the nostrils of people with

cystic fibrosis, normal CFTR protein production is

restored.

" What's remarkable about this study is that someone

has actually shown in that little patch of the nose

that they can correct the abnormality, " says

Durie of the Hospital for Sick Children in Toronto,

Canada. A larger trial where patients are inhaling the

drug is already under way.

Poor absorbtion

Gentamicin may work for other genetic diseases too. In

2002, a small trial in Italy showed the antibiotic can

restore production of the dystrophin protein in some

cases of muscular dystrophy. None of the patients

could normally make any dystrophin protein at all.

However, gentamicin has drawbacks. The body absorbs it

poorly, so it must be injected or inhaled. And

inhaling is fine for cystic fibrosis, but of little

use for conditions such as muscular dystrophy. The

antibiotic can also cause rare but serious side

effects such as hearing loss and kidney damage.

That is where PTC124 comes in: it was designed from

the start to have similar properties to gentamicin but

to be safer and more easily absorbed. " We are really

in a different situation now, where we are trying to

identify drugs based on how they should act, " says

Langdon , chief medical officer of PTC

Therapeutics in New Jersey.

The drug was screened out of a pool of 175,000

synthetic molecules. Pre-clinical tests so far

indicate that it is more potent than gentamicin and

seems to have very low toxicity. " This could have very

far-reaching effects, " claims Bedwell, a

microbiologist at the University of Alabama in

Birmingham, who has tested the compound in his lab and

is collaborating with the company.

In mice with muscular dystrophy the drug restores

expression of the dystrophin protein found on the

surface of muscle cells. Tests suggest the muscles

regain some of their normal characteristics. Tests on

mice with cystic fibrosis also suggest PTC124 restores

production of functional CFTR.

All the results remain unpublished, though researchers

working with the company say they hope to publish as

soon as intellectual property issues are resolved.

says the company hopes to start clinical trials

with healthy volunteers as early as next 2004.

But a premature stop mutation will not always be the

cause of a particular genetic disease. So even if

PTC124 or gentamicin make it to the market for

treating genetic diseases, they will not be a magical

cure for everyone.

Sylvia Pagán Westphal

--------------------------------------------------

--- Salvador Navarro wrote:

> Hello all from Spain.

> After lurking some time and learning so much from

> this list (not writing

> because is difficult for me in English and I had not

> any important things to

> say), I will try to contribute in some questions.

> I am the father of a 12 yo girl, Olaia, with cf, and

> a 15 yo boy, Alvaro,

> without. Olaia is doing great till now. She has

> deltaF508 and g542x.

>

> From what I understand Torin has three mutations: a

> CFTR gen with two

> mutations in one chromosome and one in the other.

> They don't know witch two

> are together and witch alone. That is why they want

> to study their parents.

> One of his mutations is y913x, a stop mutation. That

> means that gentamicin

> could correct the genetic defect. Olaia is on

> inhaled gentamicin since eight

> months ago (in some Spanish hospitals the protocol

> includes long term

> inhaled-gentamicine to prevent pseudomonas

> colonization). Well I can say

> that from the first moment we clearly noticed how

> the lungs were working

> better (much less coughing, and now eight months

> without a cold). The

> problem of the gentamicine are the side effects

> (possible kidney damage). It

> is known that when inhaled the side effects are much

> lower, but nobody knows

> the effect of genta when given during years. For the

> moment we follow on.

> There are some ongoing studies (Cleveland and

> Jerusalem) about genta, and

> looking for any substance with the same effects on

> the gene than gentamicin but less side effects.

>

> Salva

>

>

>