This month, research funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research Council (MRC) suggests that it is possible to reset the circadian rhythm of mammals using so called “Body Clock” drugs that inhibit the activity of casein kinase 1. This research has the potential to develop new treatments for mental disorders associated with sleep deprivation and insomnia.
A broken circadian rhythm (night-sleep/day-awake) is a diagnostic criteria for a number of psychiatric problems including a Major Depressive Episode (DSM IV) and a factor in many depressive and psychotic disorders. Sleeping tablets are frequently used to manage these symptoms and augment treatment regimes.
Leading the research, Professor Andrew Loudon described the 24 hour body clock in terms of a rising and decaying wave of wakefulness. At the peak of wakefulness, body cells contain the highest quantities of the protiens that govern the circadian rhythm. Casein kinase 1 contributes to the breakdown of these substances as the organism heads back towards sleep. The research team was able to slow down and speed up the 24 hour body clock of mice in the lab by inhibiting the action of this enzyme.
Dr. Wager, Associate Research Fellow, Pfizer, points out that "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."
Could such novel treatments be cleaner in terms of side effects than currently favoured drugs? The findings are also expected to open up possibilities for the management of jet lag and the health implications of shift work.
Findings are published this week in PNAS under Meng et al. 2010, "Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes", PNAS 107(34) p15240