Preclinical Drug Evaluations at the SCN Lab

New Opportunities for the Pharmaceutical Industry

About 100 million Americans each year complain of disturbed sleep. Many different pathophysiologiocal/etiologoical mechanisms for these sleep disorders have been recognized, and the International Classification of Sleep Disorders (ICSD) lists 81 different types of disorders under 8 main categories. These sleep-related problems are often chronic and negatively affect the subject's quality of life. In a 24-hour society that encourages sleep deprivation, daytime sleepiness is also an emerging issue even in healthy subjects. Accidents (e.g., Chernobyl nuclear accident, Three Mile Island accident, Bophal Chemical Spill, Exxon Valdes accident) due to sleepiness are now well recognized as a major public hazard.

There has never been a greater need for the development of pharmacological therapeutics for sleep-wake disorders. Indeed, the affected population that would benefit from sleep-wake therapeutics is dramatically increasing world-wide.

At Stanford University, we have established a team of research scientists and technical specialists who are dedicated to fostering joint academic-industrial research ventures in pharmaceutical research and development. We have also assembled the most technologically advanced research equipment and computer system to assay drug effects on sleep-wakefulness in laboratory animals.

The large scale of our drug screening facility greatly accelerates the process of pre-clinical drug evaluation and provides simultaneous quantitative measures of sleep and wakefulness, body temperature, motor activity and other behavioral variables useful in selecting compounds for clinical trial.

SCN Lab sleep assay system

Advantages of using the SCN lab sleep assay to screen novel compounds:

• High capacity: 64 rodents, surgically prepared for sleep-wake recordings, are continuously on-line.
• High technology: The SCN lab sleep assay constitutes the most advanced hardware and software application of its kind for sleep research.
• Unsurpassed expertise: An existing team of experienced scientists and highly trained technical specialists operate and manage the SCN lab sleep bioassay facility, in addition to a Sleep Research Center with associate experts in many aspects of pharmacology.
• Various animal models for sleep disorders and appropriate controls.
• Existing database of standard compounds.

Situations ideal for using the SCN lab sleep assay to record EEG sleep:

• Comparing novel compounds to standards in our database.
• Evaluating animal models (e.g., rodent narcolepsy models) to determine if the compounds normalize sleep abnormalities.
• Selecting one of several similar compounds to go to clinical trials.
• Distinguishing sleep from physical side effects in a novel compound.
• Selecting a compound that has least sedative side effects.
• Multiple physiological characterizations - EEG, locomotor activity, body temperature, consumatory behavior, and video behavior monitoring.
• Experiments requiring more long-term data than in-house bioassays can provide: the SCN lab's sleep bioassay routinely examines after-effects for 24 hours and easily provides additional after-effect data for weeks.
• Characterizing arousal states during repeated - dosing trials with side effects monitoring.
• Our advanced technology allows the fastest, most cost-effective approach to recording sleep.

The SCN lab sleep bioassay system is also routinely used to assess:

• Stimulants, especially in seeking non-euphoriant, non-anxiogenic compounds
• Phase-shifting agents, with potential use for shift work and jet lag
• Sedative side effects in anxiolytic compounds

Major uses for hypnotics include:

• Sleep disorders associated with aging
• Jet lag
• Shift work
• "Situational" transient insomnia (new environment, noise)
• Short-term insomnia due to stress, grief, pain, illness
• Intermittent treatment of chronic insomnia
• About 100 million Americans each year complain of disturbed sleep