The Science

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

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 due to Alzheimer’s disease (MCI due to AD), the earliest symptomatic stage characterized by memory loss. Overactivity detected by brain imaging predicts the extent of neurodegeneration in the earliest stages of MCI due to AD and clinical progression to Alzheimer’s dementia.

Brain Network Dysfunction in MCI due to AD Predicts Progression to Alzheimer’s Dementia

Hippocampal overactivity, the distinguishing characteristic of MCI due to AD, 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 MCI due to AD, the symptomatic pre-dementia stage of Alzheimer’s.

We believe that restoring the entorhinal cortex-hippocampal network is critical for symptomatic relief in MCI due to AD 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.

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 MCI due to. 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.

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Learn more from our Publications page.