NOSE-TO-BRAIN DELIVERY OF MITOCHONDRIA TARGETING DRUGS FOR THE TREATMENT OF ALZHEIMER'S DISEASE: PHARMACOKINETIC AND NEUROPHENOTYPING EVALUATION

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive impairment and pathological hallmarks such as the formation of amyloid plaques and neurofibrillary tangles, synaptic failure, and neuronal loss. The evidence supporting amyloid-beta lowering approaches as clinically viable are waning and there is an increasing number of agents which are not based on anti-amyloid mechanisms of action in earlier phases of drug development. Recent studies implicate mitochondrial abnormalities in the pathogenesis of AD. However, many potential therapeutic agents that address these abnormalities do not readily cross the blood-brain barrier (BBB) after oral administration, thus limiting their therapeutic potential in AD treatment. Intranasal delivery offers an effective and non-invasive method of bypassing the BBB to deliver therapeutic agents to the brain. We hypothesize that the use of a nasal route of administration to deliver therapeutic agents that can protect neuronal mitochondria has merit in the case of AD.