Sleep gene discovery

[Guest guest]

Sleep gene discovery

http://www.news-medical.net/?id=18706

Proteins that regulate sleep and biological timing in the body work

much differently than previously thought, meaning drug makers must

change their approach to making drugs for sleep disorders and

depression and other timing-related illnesses.

The surprise finding is an about-face from previous research, said

Forger, assistant professor of math at the University of

Michigan.

Forger and his collaborators from the University of Utah's Huntsman

Cancer Institute have written a paper on the topic, which appears in

the Proceedings of the National Academy of Science.

Scientists studied two proteins (one called CKIe and another called

PERIOD) that help regulate timing in the body, and looked at how

those proteins function in cells, said Forger. One of the proteins

causes the other protein to degrade, and the body knows what time it

is by how much or how little PERIOD protein is present at any one

time in the body. The body's clock is called a circadian rhythm.

Drug makers spend billions to develop drugs to help people with sleep

disorders, and other disorders impacted by our biological clocks.

Drugs to restore a healthy circadian rhythm by manipulating the

levels of PERIOD proteins are currently under development.

One such sleep disorder is called Familial Advanced Sleep Phase

Syndrome and this is caused by a gene mutation, Forger said. Patients

suffering from the disease routinely wake very early, say at 4 a.m.

and must go to bed early, at say 7 p.m. said Forger.

If put in a cave with no light, these people should have a shortened

day, Forger said. This means that on our time, they would wake the

first day at say, 6 a.m. then at 4 a.m. then at 2 a.m. on subsequent

days.

" When they have light and dark cycles in the normal world, they

pretty much have to live in a 24-hour day, " Forger said. " They were

able to adjust but the price they have to pay is their body wakes up

early, and they have to go to bed earlier than we do. "

" The theory was that the mutation caused (more of the PERIOD protein)

so you get a short day so you want to get up very early in the

morning, " Forger said. But, during testing they found the opposite is

true: the mutation actually caused the PERIOD to degrade more quickly

so that less is present in the body.

The finding wasn't a complete surprise to Forger, who develops math

models of the circadian rhythms. Forger's computer models always said

that the opposite of the prevailing thinking should be true---that

the PERIOD protein should degrade more quickly when the mutation is

present.

" I had this prediction for a year or two, " Forger said. " Basically,

people said this is ridiculous, you're a mathematician, what do you

know? "

Then he met Virshup, M.D., while giving an invited talk at the

University of Utah. Virshup's previous research was on the gene

involved in circadian rhythms and its role in cancer development.

Their experiments had also suggested that genetic mutation caused the

protein to degrade more quickly. Virshup suggested they test Forger's

simulation.

The researchers took cell cultures and observed that for those with

the mutated gene, the protein only took a couple hours to degrade.

For the normal gene, it took 8-10 hours.

Next, Virshup said, his team will begin testing ways to regulate the

circadian rhythm in mice, a necessary step before new drugs can be

developed.