Body clock mouse study suggests new drug potential
LONDON (Reuters) - Scientists have used experimental drugs being developed by Pfizer to reset and restart the body clock of mice in a lab and say their work may offer clues on a range of human disorders, from jetlag to bipolar disorder.
The drugs, which are not yet available in a form suitable for humans and could take many years to develop into human medicines, work by altering the activity of an enzyme which helps set the speed of the body clock.
Researchers say they could potentially restore rhythms in people whose body clocks are messed up by shift work, or in psychiatric disorders like depression, and may even have implications for metabolic problems such as obesity.
"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," said Andrew Loudon of Britain's Manchester University, who worked on the study with scientists backed by the British Medical Research Council (MRC) and others from the U.S. drugs giant Pfizer.
"The implication of this is that if you have humans with severely disrupted rhythms - and that is quite a common occurrence - these drugs could...act as potent regulators of body clock function. They're probably the first such potential drugs that could do that," he said in a telephone interview.
Most living creatures have an internal timing system - called the circadian clock and commonly known as the body clock - that drives the rhythm of everything from sleep in mammals to flowering in plants. Light, and the cycle of day and night, are important for resetting the clock, and fine adjustments are controlled by the activity of several enzymes, including one called casein kinase 1 or CK-1.
Loudon's team found that the experimental drugs, which slow down or inhibit CK-1, enabled them to restart the clock in mice whose circadian rhythm had previously stopped.
Many scientific studies have found links between working irregular hours such as night-shifts and a greater likelihood of developing diabetes, cardiovascular disease and obesity, and sleep disruption is also associated with mental illnesses such as depression and bipolar disorder.
"We're all familiar with jetlag 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," said Michel Goedert, of the neurobiology division at the MRC's laboratory of molecular biology.
"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."
The results of the experiments with the CK-1 inhibitors, called PF4800567 and PF670462, were published in the Proceedings of the National Academy of Sciences (PNAS) journal on Monday.
Travis Wager, a Pfizer scientist who worked with Loudon on the research, told Reuters the company was keen to develop a CK1 inhibitor for testing in humans and is currently in the process of selecting the most suitable drug candidate.
He said it would take around three years to get to mid-stage human clinical trials and it is likely to be several years beyond that before any drug could be approved and on the market.
SOURCE: http://link.reuters.com/nat66n Proceedings of the National Academy of Sciences, online August 23, 2010.
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