Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Body clock drugs could ease psychiatric disorders and jet lag

24.08.2010
Researchers funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research Council (MRC) have successfully used a drug to reset and restart the natural 24 hour body clock of mice in the lab. The ability to do this in a mammal opens up the possibility of dealing with a range of human difficulties including some psychiatric disorders, jet lag and the health impacts of shift work.

This work is led by Professor Andrew Loudon from the University of Manchester and Dr Mick Hastings of the MRC Laboratory of Molecular Biology in Cambridge, working with a multi-disciplinary team of scientists from Pfizer led by Dr Travis Wager, and is published today (24 August) in PNAS.

Professor Loudon said "It can be really devastating to our brains and bodies when something happens to disrupt the natural rhythm of our body clocks. This can be as a result of disease or as a consequence of jet lag or frequent changing between day and night shifts at work.

"We've discovered that we can control one of the key molecules involved in setting the speed at which the clock ticks and in doing so we can actually kick it into a new rhythm."

Most living creatures and plants have an internal body timing system – called the circadian clock. This is a complex system of molecules in every cell that drives the rhythmicity of everything from sleep in mammals to flowering in plants. Light and the day and night cycle are very important for resetting the clock and the fine adjustments are made through the action of several enzymes, including one called casein kinase 1, which has been the centre of this project.

Professor Loudon continued "The circadian clock is linked to the 24 hour day-night cycle and the major part of the clock mechanism 'ticks' once per day. If you imagine each 'tick' as represented by the rise and fall of a wave over a 24 hour period, as you go up there is an increase in the amount of proteins in the cell that are part of the clock mechanism, and as you go down, these substances are degraded and reduce again. What casein kinase 1 does is to facilitate the degradation part.

"So you can imagine that the faster casein kinase 1 works, the steeper the downward part of the wave and the faster the clock ticks - any change in casein kinase 1 activity, faster or slower, would adjust the 'ticking' from 24 hours to some other time period. Consider that if your body suddenly starts working on a 23 hour or 25 hour clock, many of your natural processes, such as sleeping and waking could soon become out of step with day and night."

The team found a drug that slows casein kinase 1 down and used it in mice where the circadian rhythm has ceased i.e. the clock has stopped ticking all together. In live mice and also in cells and tissue samples from mice, they were able to re-establish the ticking of the clock by using the drug to inhibit the activity of casein kinase 1.

Professor Loudon concluded "We've shown that it's possible to use drugs to synchronise the body clock of a mouse and so it may also be possible to use similar drugs to treat a whole range of health problems associated with disruptions of circadian rhythms. This might include some psychiatric diseases and certain circadian sleep disorders. It could also help people cope with jet lag and the impact of shift work."

Professor Janet Allen, BBSRC Director of Research said "The most effective way to develop drugs to treat a health problem is to understand the basic biology that underpins what is going on in our bodies. In this case, by understanding the basic biology of the enzyme controlling biological clocks the research team have been able to identify potential drug-based solutions to a range of issues that affect many people's health and quality of life."

Dr Michel Goedert, Head of the Neurobiology Division at Medical Research Council Laboratory of Molecular Biology said "We're all familiar with jet-lag and that sense of being disoriented in time. What is probably less widely understood is how this effect can impact on those with certain mental illnesses. It is crucial to find out what can go wrong at the molecular and cellular level in the brain if we are to determine what treatments will work for patients. If further studies in humans confirm what this study has shown in mice, this could eventually lead to an entirely new approach to treating mental illnesses such as bipolar disorder."

Dr. Wager, Associate Research Fellow, Pfizer said "It is amazing what can be accomplished when first-rate academic groups and pharmaceutical discovery units team up. Leveraging each other's talents we now have a deeper understanding of the role casein kinase plays within biological systems. Having the ability to entrain or re-entrain an arrhythmic system opens the door to new treatment option for circadian rhythm disorders. Targeting the inhibition of casein kinase with small molecules may lead to the discovery of novel drugs for the treatment of bipolar depression and other circadian rhythm disorders. The burden of these disorders is enormous and new treatment options are needed."

NOTES TO EDITORS

This research will be published in PNAS as follows:

Meng et al. 2010, "Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes", PNAS 107(34) p15240

About BBSRC

BBSRC is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £470 million in a wide range of research that makes a significant contribution to the quality of life in the UK and beyond and supports a number of important industrial stakeholders, including the agriculture, food, chemical, healthcare and pharmaceutical sectors.

BBSRC provides institute strategic research grants to the following:

The Babraham Institute, Institute for Animal Health, Institute for Biological, Environmental and Rural Studies (Aberystwyth University), Institute of Food Research, John Innes Centre, The Genome Analysis Centre, The Roslin Institute (University of Edinburgh) and Rothamsted Research. The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.

For more information see: http://www.bbsrc.ac.uk

About the Medical Research Council (MRC)

For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century www.mrc.ac.uk.

Nancy Mendoza | EurekAlert!
Further information:
http://www.bbsrc.ac.uk

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

NSF-supported researchers to present new results on hurricanes and other extreme events

19.07.2018 | Earth Sciences

Scientists uncover the role of a protein in production & survival of myelin-forming cells

19.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>