How can a new pharmaceutical treat severe sleep disturbance a new way?

TeachableMedicalNews article 01312022

Teachable moment in classrooms:

1. cellular basis of life chapter – concept of one gene, one protein
2. cellular basis of life chapter – concept of gene mutation leading to protein malfunction
3. nervous system chapter – functional roles of hypothalamus
4. nervous system chapter – sleep and wakefulness
5. endocrine system – receptor agonists enhance cellular response

The news item:  Recently a news item appeared about a new pharmaceutical to treat severe sleep disturbance disorders:

https://sleepreviewmag.com/sleep-treatments/pharmaceuticals/prescription-drugs/fda-approves-hetlioz-sleep-disturbances-smith-magenis-syndrome/

The article states that the pharmaceutical Hetlioz was approved to treat sleep disturbance disorders in adults and children, and also people suffering from Smith-Magenis syndrome.

So, Why Do I Care??  While loosing sleep hours is a common occurrence that comes with minor inconveniences in our daily lives, severe sleep disturbance, however, describes a disorder with significant health consequences. Millions of people suffer from such severe sleep disturbance in the US, and then there are over 15,000 people in the US who suffers from Smith-Magenis syndrome.

Plain English, Please!!! First let’s talk about sleep disturbances, in general. The action of going into sleep is the result of nerve signals from the hypothalamus part of the brain, and that signal decreases the activity of the cerebrum part of our brain, causing us to fall asleep. The activity of the hypothalamus is coordinated with the rising and setting of the Sun. Malfunctioning of the hypothalamus can cause sleep disturbances, because the timing of falling asleep, or the timing of waking up now no longer coordinated with daylight.

Second, let’s talk about Smith-Magenis syndrome. The cause is the missing or mutated RAI1 gene.  This disorder affects many aspects of the nervous system, and among the symptoms is sleep inversion.  Sleep inversion comes from the reversal of one of the actions of the hypothalamus, namely, the sleep-enhancing hormone, melatonin, is produced during the daytime as opposed to the normal production during night time. People with Smith-Magenis syndrome are sleepy during daytime, and have difficulty entering the restful REM stage of night time sleep.

Third, let’s talk about how Hetlioz treats sleep disturbance.  When melatonin acts on neurons of the brain to bring about sleep, melatonin binds to melatonin receptors on the surface of neurons. A receptor is like a doorbell that fits the size of the finger, melatonin. When a doorbell is pushed, the signal spreads in the house, and people will react to the signal. Neurons receive the signal of melatonin the same way. What Hetlioz does is to make the doorbell sound longer. Taken before bedtime Hetlioz enables the melatonin to signal longer on neurons, and those neurons will follow the instructions of melatonin for a longer time to go into a night time sleep behavior. The patient experiences a longer uninterrupted sleep.