Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hope on the horizon for asthma sufferers

18.09.2012
UCSF-led research team targets physiological factors that lead to asthma attack

A new study that identifies ways to reduce the factors that lead to an asthma attack gives hope to asthma sufferers. A UCSF researcher and his colleagues believe they have found a way to help asthma sufferers by impeding the two most significant biological responses that lead to an asthma attack.

Asthma, a respiratory disorder that causes shortness of breath, coughing and chest discomfort, results from changes in the airways that lead to the lungs. It affects 18.7 million adults and 7.0 million children in the US, according to the Centers for Disease Control and Prevention.

In a paper published Monday in the Proceedings of the National Academy of Sciences (PNAS), researchers from UCSF, Johns Hopkins University and Duke University demonstrate that a specific calcium-activated chloride channel holds valuable clues to reducing two biological processes that contribute to the severity of asthma. These channels regulate airway secretions and smooth muscle contraction, the two major factors that lead to an asthma attack.

"Maybe if we could inhibit both of these processes by blocking this one channel, then we could affect the two symptoms of asthma," said senior author Jason Rock, PhD, assistant professor at the UCSF Department of Anatomy.

Normally humans have few mucus-producing cells but asthma sufferers have an elevated number of these cells in the lining of the tubes that lead to the lungs. Asthmatics also have an abnormal amount of smooth muscle surrounding the airway tubes. Even the slightest stimulus can cause these to contract.

"The overabundance of mucus plugging the airways combined with hyper-contractility of the smooth muscle – when the tubes get really small – make it difficult to move air in or out," Rock said. "A lot of people equate that with breathing through a straw."

Rock and his colleagues focused on a calcium-activated chloride channel called TMEM16A. This channel secretes chloride ions in response to rises in intracellular calcium. It regulates a significant number of biological processes such as neuron firing, gastrointestinal activity and the secretion of sweat and tears.

The researchers wanted to prove that the channel was present in asthma. They studied human lung samples and looked for the mRNA (messenger RNA which carries information from the DNA to the sites of protein synthesis), and compared protein levels in asthmatic and non-asthmatic patients.

"We found that the level of this channel was increased in the mucus producing cells of asthmatics compared to non-asthmatics," Rock said. "And we also validated this in several models of asthma, including mouse models. That was step one."

Step two consisted of a screen to identify chemicals that inhibit the activity of TMEM16A. The authors identified three chemicals that inhibit the channel.

"We tested the ability of these chemicals to inhibit TMEM16A and other channels, and we found that they specifically block TMEM16A," Rock said. "It is great that we came across these molecules that were unknown previously since we can now try to get into clinical trials to benefit patients."

Then, the authors simulated asthma in a dish and blocked the channel to observe whether it affected mucus production. "Mucus produced by these cells wasn't secreted as efficiently," Rock said. "We also studied airway smooth muscles of human patients who had given their organs to science, and we could see that blocking TMEM16A inhibited their contraction response as well."

Rock is in the pre-clinical phase to test the safety and effectiveness of the blockers in animal studies. If that goes well, Phase One of clinical trials can begin.

"At present, I am optimistic," Rock said. "This could be a major advance to help asthma sufferers."

Rock is the senior author of the paper; co-authors include Fen Huang, Huanghe Yang, Makoto Kudo, Christian Peters, Prescott Woodruff, Owen Solberg, Matthew Donne, Xiaozhu Huang, Dean Sheppard, John Fahy, Paul Wolters, Walter Finkbeiner Yuh-Nung Jan, and Lily Jan of UCSF; Brigid Hogan of Duke University; and Hongkang Zhang, Meng Wu, and Min Li of Johns Hopkins University.

This study was supported by the Strategic Program for Asthma Research, the Cystic Fibrosis Foundation, the National Institutes of Health and the Howard Hughes Medical Institute.

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Follow UCSF
UCSF.edu | Facebook.com/ucsf | Twitter.com/ucsf | YouTube.com/ucsf

Leland Kim | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>