There have been some incredible breakthroughs in CF this year.
A medication commonly used for an unrelated condition (somebody
help me out -- I'm blocking on the name here) is quite halpful
for symptomatic treatment, and a retrovirus has been made to
replace the defective gene.  I believe this is now in the human
testing stage.  Very exciting work.

A twelve year old neighbor of mine has a deep voice for a girl and
coughs a lot.  I asked if she had been yelling a game or something
like that.  But no, it turns out that she has Cystic Fibrosis (CF).

Does anyone know the state of the current research on CF?
I read that CF is a genetic disorder.  Is it possible to
cure a genetic disorder?   What is the life expectancy of a  CF
patient nowadays?  (that is, assuming that she follows the instructions of the
physician.)

--
--

 From the beautiful and historic Mid-Hudson Valley area of NY state

CF is an inherited disease which is extremely common in the white population
(approx 1 in 2000) births. It is autosomal recessive. The CF gene has
been isolated and is on Chrom 7. The primary defect appears to be problems
with substance transport across cell membranes and effects cells/organs
with exocrine function.

Children with CF used to die in their {*filter*}s, however, that has been
improving and I think that recent data show CF patients living into
their late 20's. They develop progressive pulmonary problems with
recurrent infections, bronchiectasis (airways get larger, instead of
smaller as the go out, trapping mucous, bacteria, etc), hemoptysis
(coughing up {*filter*}), airway obstruction (difficulty getting air out),
cor pulmonale (essentially right heart failure from pumping {*filter*}
through diseased lungs).

Pancreatic insufficiency is very common as is sinus involvement. The
goal of therapy is to keep the lungs clear of pus and active
infection. Currently, there is no cure. Lung transplantation (not
a cure) is being performed, however conclusive data as to long-term
benefit is not available.

--

[]  University of Kentucky, Lexington, Kentucky                              []

I'm not sure whether gene therapy for humans has started yet, but
there was some very promising work using an adenovirus vector to
deliver the human CFTR (protein missing in CF patients) to rat
airway epithelium (one of the tissues that needs to express
CFTR to remain healthy).

There are lots of {*filter*} being examined now that something is known
about the CF gene product, but the one you are probably thinking of
is DNAse. DNA is very viscous and is released by all of the
dying cells (bacteria and PMNs) in the mucus. Lysing the DNA
with DNAse cuts down on the viscosity and makes it easier to
breathe. This idea is not the product of any high-tech research,
but it works.

For more info see Science 1992 vol 256 page 774.
Or contact the CF society.

Brian

I'm not sure if human trials of gene replacement are underway, but
there was a promising experiment in which the human CFTR gene (gene
defective in CF patients) was delivered to rat airway epithelium
(cells in which expression of CFTR is important) using an
adenovirus vector.

Now that the CFTR is in hand, there are lots of {*filter*} being looked
at as possible therapeutics for CF. The one you are probably thinking
of is DNAse, however. The mucus of CF patients is very viscous in
part because the lysis of bacteria and PMNs in the mucus releases
lots of DNA (which is very viscous). DNAse lyses that DNA and
reduces the viscosity, making it easier to breathe. This is
not a product of high-tech research but it works.

For more info contact the CF society or see Science 1992, vol 256,
page 774.

Brian

I think you're thinking of nebulized solutions of DNAase, an enzyme
which simply digests free DNA, a molecule which is long and tangly and
hence viscous, and which is a common component of the mucus and other
crud which tends to form and collect in the lungs of CF patients due to
their underlying condition.  It's roughly the same idea as the use of
acetylcysteine, except that acetylcysteine works mainly to liquefy
mucoproteins.  I'll bet DNAase smells better (it is said that
acetylcysteine has an unbearably vile odor, one reason it is such a
trial to have to inhale a solution of it.)

--
Steve Dyer

It is definitely not possible to treat the cause of the illness, i.e.
the genetic disorder. CF is caused by a monogenetic defect on the long
branch of chromosome no. 7, which is found in every single cell of the
body.

The problem is that the death is caused by a chronic hypoxia, which results
in a pulmonary hypertension and a successive strain of the right heart. So
the life expectancy is generally influenced by the heart status. My book says
that about 60% of all newborn patients with CF will reach the {*filter*} age
(i.e. 20-30 years) when cared for intensively.

Reagards, gero.

--

     The last I heard was that a gene therapy experiment showed promise
in vitro and, I think, in animal studies, and was awaiting approval for
clinical trials.  I don't know whether it has actually progressed to
clinical trials, though, and I would be interested in reading what
anyone knows about the status of this experiment.
     The technique apparently uses an altered retrovirus as a vector
for the correct gene that is damaged in people with cystic fibrosis.

--

                                -Daniel R. Field