Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Potential New Drug Target for Cystic Fibrosis

Published: Friday, September 13, 2013
Last Updated: Friday, September 13, 2013
Bookmark and Share
Large-scale screen also identified genes not previously linked to the disease.

Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg and Regensburg University, both in Germany, and the University of Lisboa, in Portugal, have discovered a promising potential drug target for cystic fibrosis.

Their work, published online in Cell, also uncovers a large set of genes not previously linked to the disease, demonstrating how a new screening technique can help identify new drug targets.

Cystic fibrosis is a hereditary disease caused by mutations in a single gene called CFTR. These mutations cause problems in various organs, most notably making the lining of the lungs secrete unusually thick mucus.

This leads to recurrent life-threatening lung infections, which make it increasingly hard for patients to breathe. The disease is estimated to affect 1 in every 2500-6000 newborns in Europe.

In patients with cystic fibrosis, the mutations to CFTR render it unable to carry out its normal tasks. Among other things, this means CFTR loses the ability to control a protein called the epithelial sodium channel (ENaC).

Released from CFTR’s control, ENaC becomes hyperactive, cells in the lungs absorb too much sodium and - as water follows the sodium - the mucus in patients’ airways becomes thicker and the lining of the lungs becomes dehydrated.

The only drug currently available that directly counteracts a cystic fibrosis-related mutation only works on the three percent of patients that carry one specific mutation out of the almost 2000 CFTR mutations scientists have found so far.

Thus, if you were looking for a more efficient way to fight cystic fibrosis, finding a therapy that would act upon ENaC instead of trying to correct that multitude of CFTR mutations would seem like a good option.

But unfortunately, the drugs that inhibit ENaC, mostly developed to treat hypertension, don’t transfer well to cystic fibrosis, where their effects don’t last very long. So scientists at EMBL, Regensburg University and University of Lisboa set out to find alternatives.

“In our screen, we attempted to mimic a drug treatment,” says Rainer Pepperkok, whose team at EMBL developed the technique, “we’d knock down a gene and see if ENaC became inhibited.”

Starting with a list of around 7000 genes, the scientists systematically silenced each one, using a combination of genetics and automated microscopy, and analyzed how this affected ENaC.

They found over 700 genes which, when inhibited, brought down ENaC activity, including a number of genes no-one knew were involved in the process. Among their findings was a gene called DGKi.

When they tested chemicals that inhibit DGKi in lung cells from cystic fibrosis patients, the scientists discovered that it appears to be a very promising drug target.

“Inhibiting DGKi seems to reverse the effects of cystic fibrosis, but not block ENaC completely,” says Margarida Amaral from the University of Lisboa, “indeed, inhibiting DGKi reduces ENaC activity enough for cells to go back to normal, but not so much that they cause other problems, like pulmonary oedema.”

These promising results have already raised the interest of the pharmaceutical industry and led the researchers to patent DGKi as a drug target, as they are keen to explore the issue further, searching for molecules that strongly inhibit DGKi without causing side-effects.

“Our results are encouraging, but these are still early days,” says Karl Kunzelmann from Regensburg University. “We have DGKi in our cells because it is needed, so we need to be sure that these drugs are not going to cause problems in the rest of the body.”


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

DNA Protection, Inch by Inch
DNA within reproductive cells is protected through a clever system of find and destroy: new lifts the veil on how this is done.
Monday, July 13, 2015
Cells Keep to One Direction by Erasing the Path
Findings could have implications for cancer and metastasis.
Tuesday, October 01, 2013
Of Flies and Men
What 10 000 fruit flies have to tell us about differences between the sexes.
Monday, July 23, 2012
Blood-clotting Protein Linked to Cancer and Septicaemia
In our not-so-distant evolutionary past, stress often meant imminent danger, and the risk of blood loss, so part of our body’s stress response is to stock-pile blood-clotting factors.
Friday, February 04, 2011
Making Enough Red Blood Cells
EMBL scientists identify molecules that ensure red blood cell production
Tuesday, June 01, 2010
Movies for the Human Genome
EMBL scientists identify the genes involved in cell division in humans
Thursday, April 01, 2010
EMBL Scientists Take New Approach to Predict Gene Expression
Thanks to scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, it is now possible to accurately predict when and where different CRMs will be active. The study, published today in Nature, is a first step towards forecasting the expression of all genes in a given organism and demonstrates that the genetic regulation that is crucial for correct embryonic development is more flexible than previously thought.
Thursday, November 05, 2009
Raising the Alarm When DNA Goes Bad
EMBL scientists identify a rapid response team that monitors and quickly responds to DNA damage.
Monday, August 17, 2009
Scientific News
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Watching a Tumour Grow in Real-Time
Researchers from the University of Freiburg have gained new insight into the phases of breast cancer growth.
Childhood Cancer Cells Drain Immune System’s Batteries
Cancer cells in neuroblastoma contain a molecule that breaks down a key energy source for the body’s immune cells, leaving them too physically drained to fight the disease.
Urine Proteins Point to Early-Stage Pancreatic Cancer
A combination of three proteins found at high levels in urine can accurately detect early-stage pancreatic cancer, researchers at the BCI have shown.
Researcher Discovers Trigger of Deadly Melanoma
New research sheds light on the precise trigger that causes melanoma cancer cells to transform from non-invasive cells to invasive killer agents, pinpointing the precise place in the process where "traveling" cancer turns lethal.
Genetic Tug of War
Researchers have reported on a version of genetic parental control in mice that is more targeted, and subtle than canonical imprinting.
Error Correction Mechanism in Cell Division
Cell biologists have reported an advance in understanding the workings of an error correction mechanism that helps cells detect and correct mistakes in cell division early enough to prevent chromosome mis-segregation and aneuploidy, that is, having too many or too few chromosomes.
How to Become a Follicular T Helper Cell
Uncovering the signals that govern the fate of T helper cells is a big step toward improved vaccine design.
Researchers Resurrect Ancient Viruses
Researchers at Massachusetts Eye and Ear and Schepens Eye Research Institute have reconstructed an ancient virus that is highly effective at delivering gene therapies to the liver, muscle, and retina.
Cell Aging Slowed by Putting Brakes on Noisy Transcription
Experiments in yeast hint at ways to extend life of some human cells.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!