The Science

Hippocampal overactivity is a key driver of aMCI: We believe that restoring the entorhinal cortex-hippocampal network is critical for symptomatic relief in aMCI.

Our novel pipeline of therapies for neurological and psychiatric disease is based on the decades of research at Johns Hopkins University and leading research centers worldwide showing that overactivity in the hippocampus contributes to cognitive impairment and drives neurodegeneration if not controlled.

This overactivity is a characteristic feature of amnestic mild cognitive impairment (aMCI) due to Alzheimer’s disease (or prodromal AD), the earliest symptomatic stage characterized by memory loss. Overactivity detected by brain imaging predicts the extent of neurodegeneration in the earliest stages of aMCI and clinical progression to Alzheimer’s dementia.


Brain Network Dysfunction in aMCI Predicts Progression to Alzheimer’s Dementia

Hippocampal overactivity, the distinguishing characteristic of aMCI, has been shown to be the best predictor of subsequent cognitive decline and conversion to Alzheimer’s dementia. Entorhinal cortex neurons are the first to degenerate in Alzheimer’s disease, beginning in aMCI, the symptomatic pre-dementia stage of Alzheimer’s.

We believe that restoring the entorhinal cortex-hippocampal network is critical for symptomatic relief in aMCI and slowing progress to Alzheimer’s dementia.

Increased metabolism, altered excitatory and/or inhibitory balance in the MCI brain may all contribute to increased excitability in turn leading to greater metabolic demand, and ultimately progressive degeneration and AD, if not controlled.

Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer’s disease. Berchtold. Neurobiology of Aging. 2014.

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Clinical Support

A Phase 2 randomized, placebo-controlled study with our lead therapeutic has shown that reducing excess hippocampal activity to a normal range improved cognition in elderly patients with aMCI. Additional publications from other scientists have confirmed the benefit of targeting excess neuronal activity in the hippocampus in basic research models of Alzheimer’s disease.


The HOPE4MCI Phase 3 clinical study with AGB101 is expected to initiate in 2017.

Learn more from our Publications page.