Piromelatine in Alzheimer Disease
Alzheimer’s disease, the leading cause of dementia in the elderly population, currently affects more than 5 million Americans and more than 40 million people worldwide, and these numbers are growing rapidly. In addition to cognitive impairment, patients suffering from Alzheimer’s disease often suffer from poor sleep and circadian rhythms control.
Piromelatine’s novel, multi-targeted mechanism of action represents new thinking on Alzheimer’s Disease pathogenesis and holds potential breakthrough benefits in sleep disorders and Alzheimer’s Disease. Due to its multimodal mechanism, it is expected to improve memory and mood, and increase cognition and neurogenesis in addition to its proven effect of improving sleep, circadian rhythms control, enhance slow-wave sleep and reduce wakefulness during the night.
Mode of Action:
Melatonin MT1, 2, and 3 and serotonin 5-HT-1A and -1D receptors agonist. Simultaneous activation of melatonergic and 5HT 1a receptors may synergistically promote neurogenesis. Melatonin receptor agonism, which maintains the NREM SWS, appears beneficial for cognition and functioning in mild to moderate AD patients.
In preclinical studies in cell and animal models of Alzheimer’s Disease, Piromelatine was found to protect from neural damage, facilitate memory performance and improve cognitive impairment and attenuate Alzheimer’s disease risk factors such as insulin resistance, hypertension and sleep disorders.
Neurim has already completed a Phase II study with Piromelatine for insomnia, in which the drug has demonstrated dose-dependent efficacy in improving sleep maintenance, and a good safety profile.
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