Novel pro-neurogenic compound that lowers synaptic

Aβ generation shows cognitive benefit and reduced hippocampal levels of insoluble and

oligomeric Aβ in vivo in an Alzheimer’s mouse model

Sam Gandy, M.D., Ph.D.Mount Sinai Chair in Alzheimer’s Disease Research

Mount Sinai School of Medicine andJames J Peters VA Medical Center

in collaboration withBrainCells, Inc.

Alzheimer’s Disease InternationalMarch 8, 2012

Baseline 78 wks Bapineuzumab Rx

Might there be a safe and novel intervention that

arrests progression of amyloidosis, enhances cognitive function, and

stimulates hippocampal repair (neurogenesis)?

Synaptic accumulation of Aβ42 is proposed to bea major mechanism in cause/progression of AD:

Is metabotropic (mGluR) signaling involved in regulating Aβ42 metabolism at the synapse?

“Synaptosome” or “synaptoneurosome”

DCG-IV stimulatesgeneration of Aβ42

but not Aβ40

Pretreatment with mGluR2/3 antagonist

blocks DCG-IV stimulatedgeneration of Aβ42

Might there be a safe and novel intervention that

arrests progression of amyloidosis, enhances cognitive function, and

stimulates hippocampal repair (neurogenesis)?

mGluR2/3 antagonist BCI-838 (632) reduces levels of

various Aβconformers in hippocampus and cortex

Might there be a safe and novel intervention that

arrests progression of amyloidosis, enhances cognitive function, and

stimulates hippocampal repair (neurogenesis)?

mGluR2/3 antagonist BCI-838 (632) corrects Aβ-induced contextual memory deficits

mGluR2/3 antagonist BCI-838 (632) improves novel object recognition,reduces anxiety in APP transgenic mice

Might there be a safe and novel intervention that

arrests progression of amyloidosis, enhances cognitive function, and

stimulates hippocampal repair (neurogenesis)?

mGluR2/3 antagonist BCI-838 (632)stimulates birth of new hippocampal neurons

Black/brown specks are

new hippocampal neurons born in response

to BCI-838 therapy

Summary

mGluR2/3 antagonist BCI-838 (632) is an

Aβ-loweringpro-cognitive, andpro-neurogenic compound

that may constitute a novel approach to early stages of Alzheimer’s disease that combines arrest of progression of amyloid pathology with stimulation of cognitive function and hippocampal repair (neurogenesis).

Michelle Ehrlich

Soong Ho Kim

John Steele

Loren Khan

JustineBonet