The researchers
discovered a protein called VCP/pr97 which is a protein containing
valosin. The protein overpowers and kills a chloride transporter inside
the cells. Most cystic fibrosis patients have a problem of the VCP/pr97
protein, which blocks the chloride transport. When the researchers used
RNA interference, which silenced or quieted the protein, it allowed the
cells to restore the transport of chloride going in and out of the cell.
If chloride does
not move in and out of the cells, there is a buildup of thick and sticky
mucous that can be found in the pancreas, and the lungs. This build up
can cause malnutrition and chronic lung infections and even lung damage.
The researcher’s goal is to correct the chloride transport mechanism to
alleviate all symptoms of cystic fibrosis.
In everyone’s
body, there is a built-in quality check system inside cells, called ERAD,
which stands for endoplasmic reticulum-associated degradation. The
cells will detect chemically any defects in a protein. The ERAD system
sends orders to destroy and dispose of these defective proteins. The
proteasome is the location where the cells dispose of the defective
proteins.
Cystic fibrosis
people have genetic defects in a protein called CFTR, which stands for
cystic fibrosis transmembrane regulator. The ERAD system in cystic
fibrosis people have been disturbed which makes it so that the cells are
not able to successfully seek out and destroy the defective CFTR
protein.
“We were able to
confirm that to get rid of the defective CFTR protein, cells deploy VCP/p97
protein, which latches onto the damaged CFTR and sends it to the
proteasome for destruction,” Zeitlin says. “Using RNA interference,
which basically works by silencing the expression of genes or proteins,
we homed in on VCP and blocked its production. That let the defective
CFTR to successfully sneak past the quality control and race up to the
surface.”
“Targeting VCP, we
were able to achieve two things at once -- restoring chloride channel
function and curbing inflammation” said co-author Neeraj Vij, Ph.D., a
postdoctoral fellow at the Children’s Center. “Inhibiting specific sites
in VCP can lead to the development of CF drugs.”
“The goal is to
develop small molecules that disrupt the binding between the VC protein
and CFTR, much like tiny guided missiles that take out portions of this
rampant VC protein before it latches onto CFTR,” Zeitlin said.
While the RNA
interference treatment for cystic fibrosis is in its very earliest
stages, there is great potential for developing a successful RNA
interference treatment in the years to come. Once the treatment finally
make it to market (which could be many years), it could alleviate the
detrimental effects of this genetic disorder. It is estimated that
cystic fibrosis effects every one out of every 3,300 live births.
Nicole Wilson
Best Syndication
Books on Cystic Fibrosis
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