(Press-News.org) 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."
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 DGKι 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."
INFORMATION:
The search for genes that regulate ENaC was undertaken as part of the EU-funded TargetScreen2 project.
Potential new drug target for cystic fibrosis
Large-scale screen also identified genes not previously linked to the disease
2013-09-13
ELSE PRESS RELEASES FROM THIS DATE:
SARS virus treatments could hold the key for treatment of MERS-CoV outbreak
2013-09-13
Camden, UK, September 13, 2013 – A new type of coronavirus, the Middle East Respiratory Syndrome Coronavirus, MERS-CoV, was first found a year ago in a patient who died. It took several months before it was discovered that a new virus had emerged. New cases have been reported from Jordan, Qatar, Saudi Arabia, and the United Arab Emirates). France, Germany, Italy, Tunisia and the United Kingdom have reported imported cases coming from the Middle East. The virus has since been identified in just over 90 patients infected in the Middle East of which approximately 50% have ...
'Terminator' polymer that regenerates itself
2013-09-13
VIDEO:
Scientists report the first self-healing thermoset elastomer that requires no intervention to induce its repair. Taken from the following paper: A Rekondo et al, Mater. Horiz., 2014, http://xlink.rsc.org/?doi=10.1039/c3mh00061c...
Click here for more information.
Scientists in Spain have reported the first self-healing polymer that spontaneously and independently repairs itself without any intervention. The new material could be used to improve the security and lifetime ...
CO2-hungry microbes might short-circuit the marine foodweb
2013-09-13
The smallest of the small seem to be among the winners in the ocean of the future. In a five-week long experiment, an international team of scientists showed that particularly tiny plankton, so-called pico- and nanophytoplankton, grows more strongly under elevated carbon dioxide levels and produces more organic carbon. "If the tiny plankton booms, it consumes the nutrients that are normally also available to larger plankton species", explains Prof. Ulf Riebesell from GEOMAR, head of the KOSMOS mesocosm experiments. "We could clearly see that the boom at the base of the ...
NRL achieves highest open-circuit voltage for quantum dot solar cells
2013-09-13
WASHINGTON--U.S. Naval Research Laboratory (NRL) research scientists and engineers in the Electronics Science and Technology Division have demonstrated the highest recorded open-circuit voltages for quantum dot solar cells to date. Using colloidal lead sulfide (PbS) nanocrystal quantum dot (QD) substances, researchers achieved an open-circuit voltage (VOC) of 692 millivolts (mV) using the QD bandgap of a 1.4 electron volt (eV) in QD solar cell under one-sun illumination.
"These results clearly demonstrate that there is a tremendous opportunity for improvement of open-circuit ...
Inheritance of lifespan is sex-dependent in fruit flies
2013-09-13
This news release is available in German. Like mother, like daughter; like father, like son. Evolutionary biologists at the universities in Bielefeld (Germany) and Uppsala (Sweden) have now shown that this proverb also applies to inheriting a long life – at least for fruit flies (Drosophila). The research team found that the descendants of these insects mostly inherit their lifespan from their own sex: male descendants will very probably live about as long as their fathers; female descendants, about as long as their mothers. The scientists have published their findings ...
Young people choose education based on parents' background
2013-09-13
Even though Danish students have equal access to education, their choice of studies is still influenced by social class. Young people from working class backgrounds are motivated by studies with a clear job profile and high income, while prestige and studies with a strong identity appeal to young people of parents with university degrees when choosing which studies to pursue. This is what researchers from the University of Copenhagen conclude in a new study.
Students who have chosen to study medicine, architecture, economy and sociology often come from homes where the ...
Vaccination with GM2-KLH-QS21 does not improve outcome of melanomas patients in EORTC study
2013-09-13
Results of an EORTC study published in the Journal of Clinical Oncology show that vaccination with GM2/KLH-QS-21 does not benefit patients with stage II melanoma. Vaccination with GM2/KLH-QS-21 stimulates the production of antibodies to the GM2 ganglioside, an antigen expressed by many melanomas. Serological response to GM2 was shown to be a positive prognostic factor in patients with melanoma and was the rationale for this trial.
The idea of treating cancer with a vaccine has been around since the first vaccines against infectious disease were developed. The GM2 ganglioside, ...
Fate of new genes cannot be predicted
2013-09-13
New versions of genes, called alleles, can appear by mutation in populations. Even when these new alleles turn the individuals carrying them more fit to survive and reproduce, the most likely outcome is that they will get lost from the populations. The theory that explains these probabilities has been postulated by the scientist J.B.S. Haldane almost 90 years ago. This theory has become the cornerstone of modern population genetics, with studies on adaptation to novel environments and conservation of species, for example, being based on it. However, until now there were ...
Researchers use machine learning to boil down the stories that wearable cameras are telling
2013-09-13
Computers will someday soon automatically provide short video digests of a day in your life, your family vacation or an eight-hour police patrol, say computer scientists at The University of Texas at Austin.
The researchers are working to develop tools to help make sense of the vast quantities of video that are going to be produced by wearable camera technology such as Google Glass and Looxcie.
"The amount of what we call 'egocentric' video, which is video that is shot from the perspective of a person who is moving around, is about to explode," said Kristen Grauman, ...
EORTC at 2013 ECCO-ESMO-ESTRO meeting in Amsterdam
2013-09-13
The EORTC will have an active presence at the 2013 ECCO-ESMO-ESTRO Meeting in Amsterdam, The Netherlands, from 27 September to 01 October 2013 and would like to call your attention to the following presentations.
Society Session
F. Meunier and R. Stupp are co-Chairs of the session "European Organisation for Research and Treatment of Cancer (EORTC) - Multidisciplinary Cancer Clinical Research: What are we up to in 2013?" on Saturday, 28 September 2013 from 16:00 - 18:00 in Room G102.
Special sessions
J. Bogaerts will chair a Special session, "Dilemma of Crossover ...
LAST 30 PRESS RELEASES:
Shaking it up: An innovative method for culturing microbes in static liquid medium
Greener and cleaner: Yeast-green algae mix improves water treatment
Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac
CIDEC as a novel player in abdominal aortic aneurysm formation
Artificial intelligence: a double-edged sword for the environment?
Current test accommodations for students with blindness do not fully address their needs
Wide-incident-angle wideband radio-wave absorbers boost 5G and beyond 5G applications
A graph transformer with boundary-aware attention for semantic segmentation
C-Path announces key leadership appointments in neurodegenerative disease research
First-of-its-kind analysis of U.S. national data reveals significant disparities in individual well-being as measured by lifespan, education, and income
Exercise programs help cut new mums’ ‘baby blues’ severity and major depression risk
Gut microbiome changes linked to onset of clinically evident rheumatoid arthritis
Signals from the gut could transform rheumatoid arthritis treatment
Pioneering research reveals some of the world’s least polluting populations are at much greater risk of flooding fuelled by climate change
UK’s health data should be recognized as critical national infrastructure, says independent review
A 36-gene predictive score of anti-cancer drug resistance anticipates cancer therapy outcomes
Someone flirts with your spouse. Does that make your partner appear more attractive?
Hourglass-shaped stent could ease severe chest pain from microvascular disease
United Nations ratifies framework to protect people on cash app
Oklahoma State basketball team joins the Nation of Lifesavers
Power of aesthetic species on social media boosts wildlife conservation efforts, say experts
Researchers develop robotic sensory cilia that monitor internal biomarkers to detect and assess airway diseases
Could crowdsourcing hold the key to early wildfire detection?
Reconstruction of historical seasonal influenza patterns and individual lifetime infection histories in humans based on antibody profiles
New study traces impact of COVID-19 pandemic on global movement and evolution of seasonal flu
Presenting a Janus channel of membranes for complete oil-and-water separation
COVID-19 restrictions altered global dispersal of influenza viruses
Disconnecting hepatic vagus nerve restores balance to liver and brain circadian clocks, reducing overeating in mice
Mechanosensory origins of “wet dog shakes” – a tactic used by many hairy mammals – uncovered in mice
New study links liver-brain communication to daily eating patterns
[Press-News.org] Potential new drug target for cystic fibrosisLarge-scale screen also identified genes not previously linked to the disease