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Novel pro-neurogenic compound that lowers synaptic A β  generation shows cognitive benefit and reduced hippocampal levels of insoluble and oligomeric.

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Presentation on theme: "Novel pro-neurogenic compound that lowers synaptic A β  generation shows cognitive benefit and reduced hippocampal levels of insoluble and oligomeric."— Presentation transcript:

1 Novel pro-neurogenic compound that lowers synaptic A β  generation shows cognitive benefit and reduced hippocampal levels of insoluble and oligomeric A β  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 and James J Peters VA Medical Center in collaboration with BrainCells, Inc. Alzheimer’s Disease International March 8, 2012

2 Baseline78 wks Bapineuzumab Rx

3 Might there be a safe and novel intervention that arrests progression of amyloidosis, enhances cognitive function, and stimulates hippocampal repair (neurogenesis)?

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5 Synaptic accumulation of A β 42 is proposed to be a major mechanism in cause/progression of AD: Is metabotropic (mGluR) signaling involved in regulating A β 42 metabolism at the synapse?

6 “Synaptosome” or “synaptoneurosome”

7 DCG-IV stimulates generation of A β 42 but not A β 40 Pretreatment with mGluR2/3 antagonist blocks DCG-IV stimulated generation of A β 42

8 Might there be a safe and novel intervention that arrests progression of amyloidosis, enhances cognitive function, and stimulates hippocampal repair (neurogenesis)?

9 mGluR2/3 antagonist BCI-838 (632) reduces levels of various Aβ  conformers in hippocampus and cortex

10 Might there be a safe and novel intervention that arrests progression of amyloidosis, enhances cognitive function, and stimulates hippocampal repair (neurogenesis)?

11 mGluR2/3 antagonist BCI-838 (632) corrects A β -induced contextual memory deficits

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

13 Might there be a safe and novel intervention that arrests progression of amyloidosis, enhances cognitive function, and stimulates hippocampal repair (neurogenesis)?

14 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

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16 Summary mGluR2/3 antagonist BCI-838 (632) is an A β  -lowering pro-cognitive, and pro-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).

17 Michelle Ehrlich Soong Ho Kim John Steele Loren Khan Justine Bonet

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