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Discovery of activity-dependent principle underlying synaptic density regulation

Properties of synaptic transmission at single hippocampal synaptic boutons

Liu and Tsien, Nature, 1995

Importance of NR2B-NMDAR in synaptic plasticity and memory is elucidated from transgenic “Doogie” mice

Genetic enhancement of learning and memory in mice

Tang et al., Nature, 1999

Neuronal intracellular Mg2+ identified as a 2nd messenger controlling synaptic plasticity and density

Enhancement of Synaptic Plasticity through Chronically Reduced Ca2+ Flux during Uncorrelated Activity

Slutsky et al. Neuron, 2004

Enhancement of Learning and Memory by Elevating Brain Magnesium

Slutsky et al. Neuron, 2010

Regulation of density of functional presynaptic terminals by local energy supply

Zhou and Liu. Mol Brain, 2015

L-TAMS identified as drug candidate that increases structural / functional synapse density and promotes neurogenesis

Enhanced learning and memory in young and aged rats

Slutsky et al. Neuron, 2010

Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer’s disease mouse model

Li et al., Mol Brain, 2014

Increased NR2B-NMDAR pathway in rats

Slutsky et al. Neuron, 2010

Abumaria et al. J Neurosci, 2011

 Facilitated removal of fear memory and reduced anxiety

Abumaria et al. J Neurosci, 2011

Abumaria et al., Behav pharma, 2013

Facilitated rejuvenation of the adult visual cortex, providing a new avenue to develop clinical therapies for adult      amblyopia

Liu et al., Mol brain, 2015

MOA is mediated by mitochondrial energy production enhancement and movement of Ca++ sensitive proteins to terminals

Zhou et al., Mol brain, 2015

L-threonate is critical for mechanism of action

Sun et al., Neuropharmacology, 2016

Positive results from L-TAMS in human trial in MCI patients (double-blind placebo-controlled)

Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

Liu et al., Journal of Alzheimer’s Disease, 2015

Positive preliminary clinical trial results for L-TAMS tested in mild-moderate AD patients

An 8-week open label trial of L-Threonic Acid Magnesium Salt in patients with mild to moderate dementia

Wroolie, et al, Personalized Med Psych, 2017

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