Sep 142013
 

pr12sep13_m

“Inhibiting DGKi seems to reverse the effects of cystic fibrosis”

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 today 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 analysed 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.”

Read more . . .

 

The Latest on: Cystic fibrosis
  • The World Cystic Fibrosis Market Observation with Key Company Profiles – Forecast to 2022
    on November 18, 2017 at 12:28 am

    Global Cystic Fibrosis provide overview of key players and their strategic profiling in the market, comprehensively analyzing their core competencies, and drawing a competitive landscape for the market Cystic fibrosis (CF) is a genetic disorder that ... […]

  • New In-vitro Model to Help Develop Drugs for Cystic Fibrosis
    on November 17, 2017 at 2:49 am

    A new laboratory model of the infection- and inflammation-plagued airways of cystic fibrosis (CF) patients has been developed by a research team at UNC School of Medicine. The model, described in the American Journal of Respiratory and Critical Care ... […]

  • Mom Loses Daughter To Cystic Fibrosis, Raises Awareness, Funding
    on November 16, 2017 at 5:59 pm

    SOUTHOLD, NY — Three years ago, Janet Auer, who works at the Southold Free Library, faced a pain no parent should ever have to bear. Her daughter, Ericka, 18, died from cystic fibrosis. And now, the library and community that love Auer and her family ... […]

  • Global Cystic Fibrosis Partnering 2010 to 2017
    on November 16, 2017 at 3:25 pm

    The Global Cystic Fibrosis Partnering Terms and Agreements since 2010 report provides understanding and access to partnering deals and agreements entered into by the world's leading healthcare companies. LONDON, Nov. 16, 2017 /PRNewswire/ -- Download the ... […]

  • Doctors Developed A New Way To Treat Cystic Fibrosis
    on November 15, 2017 at 7:57 am

    For some sufferers of cystic fibrosis, a genetic condition that causes the lungs to fill with mucus, making it difficult for them to breathe, even a whole cocktail of medication fails to adequately control the condition. One 53 year old patient, named Els ... […]

  • Cystic Fibrosis - Global Clinical Trials Review, H2, 2017 - Research and Markets
    on November 15, 2017 at 2:11 am

    The "Cystic Fibrosis Global Clinical Trials Review, H2, 2017" clinical trials has been added to Research and Markets' offering. The clinical trial report, Cystic Fibrosis Global Clinical Trials Review, H2, 2017" provides an overview of Cystic Fibrosis ... […]

  • Cystic Fibrosis’ 65 Roses Gala raises $400,000
    on November 13, 2017 at 11:04 am

    FLOWER POWER: Sanjeev Parsad and Colleen Kohse fronted the 17th staging of Cystic Fibrosis’ 65 Roses Gala. The foundation’s signature soiree was held at the Fairmont Waterfront Hotel. Hosted by CBC’s Gloria Macarenko and Belle Puri, the party’s ... […]

  • I have cystic fibrosis - without a double lung transplant I will die
    on November 12, 2017 at 4:00 am

    I have cystic fibrosis and recently my digestive system and lungs have gone into respiratory failure. I'm on the critical list for a double lung transplant. I have to sleep with my phone on and can't leave Auckland; once I get the call I have two hours to ... […]

  • St. Cloud St. Volleyball's Krenz Battles Cystic Fibrosis
    on November 7, 2017 at 3:28 pm

    St. Cloud St. red-shirt sophomore defensive specialist Clara Krenz (North St. Paul HS) battles cystic fibrosis, which is a genetic disease that causes persistent lung infections. KSTP Sports' Darren Wolfson recently went to St. Cloud to get to know Krenz ... […]

  • Cystic Fibrosis: 5 Ways to Help Your Child Live a Longer, Healthier Life
    on November 7, 2017 at 5:26 am

    Cystic fibrosis is a lung disease that once claimed children’s lives before they started school. Thanks to advances in treatment, children with cystic fibrosis survive well into their 30s, 40s and beyond. Good care for cystic fibrosis begins with detection. […]

via Google News and Bing News

The Latest on: Cystic fibrosis

Other Interesting Posts

Leave a Reply

%d bloggers like this: