Piromelatine (also known as Neu-P11) is an investigational therapy being developed by Neurim Pharmaceuticals to manage sleeping difficulties. The compound is now being studied for its potential to improve cognitive function and slow the progression of Alzheimer’s disease by promoting better sleep.

How Piromelatine works

Sleeping, wakefulness, metabolism and body temperature are regulated through a daily cycle known as the circadian rhythm, also referred to as the “body clock.” Melatonin is a chemical that plays a key role in inducing sleep and synchronizing the sleep-wake cycle. It is also involved in learning and memory.

Many Alzheimer’s patients have a disrupted circadian rhythm, causing them to experience a variety of sleeping problems, such as sleeping longer than usual and waking up frequently throughout the night. Interrupted sleep may also lead to a buildup of toxins harmful to the brain, worsening disease symptoms.

Piromelatine is an oral treatment that improves sleep by modifying different chemical systems in the brain. For example, by stimulating melatonin receptors 1 (MT1) and 2 (MT2), Piromelatine can promote sleep. It can also improve memory, enhance mood, and reduce nighttime wakefulness by stimulating the serotonin receptor 5-HT1A. Its combined activity on both melatonin and serotonin receptors may help stimulate neuron growth in the brain.

Piromelatine in clinical trials

In mouse models of Alzheimer’s disease, a single injection of Piromelatine into the brain improved cognitive functions and memory, and provided protection against neuron death. Separate animal studies also support the effectiveness of Piromelatine in treating sleep disturbances.

In 2015, Neurim launched the ReCOGNITION study, a Phase 2 clinical trial (NCT02615002) to determine a Piromelatine dose that can effectively improve cognitive performance, as well as its safety and tolerability in patients with mild Alzheimer’s disease.

The study is enrolling an estimated 500 patients being given a daily dose of either 5 mg, 20 mg, or 50 mg of Piromelatine or placebo for six months. Assessments will be made on patients’ change of cognitive function and ability to perform normal daily activities. The study states that it is still enrolling eligible patients at sites across the U.S., but it’s reported end date is March 2018. Information is available here.

Further details

Piromelatine is classified as a new chemical entity by the U.S. Food and Drug Administration (FDA), a designation given to compounds that contain active components not found in other FDA-approved drugs.

Piromelatine has been tested in Phase 1 (NCT01114126) and Phase 2 (NCT01489969) clinical trials in patients with primary insomnia (difficulty sleeping). The treatment was able to induce deeper sleep with fewer awakenings, and was safe and well-tolerated, with no effects on mental performance the next day.

Piromelatine was also evaluated in a Phase 2 clinical trial (NCT01558284) in patients with diarrhea-predominant irritable bowel syndrome.

Other studies on mice have shown that by treating chronic sleep deprivation, Piromelatine may improve impaired metabolic profiles and the body’s response to insulin (a hormone that controls blood sugar levels), reducing the risk of conditions such as type 2 diabetes, high blood pressure, and obesity.

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