(MENAFN- JCN NewsWire) Without Significant Effects on Synaptic Function in Brain by Spinal Densitiy Evaluation at Effective Dose to Decrease Amyloid Beta Level in Cerebrospinal Fluid at Alzheimer's Association International Conference (AAIC) 2019
TOKYO, Jul, 18 2019 - (JCN Newswire) -Eisai Co.,Ltd. announced its latest data of nonclinical research which examined the effect to the synaptic function in the brain by spinal densities(1) in regard to oral BACE (beta-site amyloid precursor protein cleaving enzyme) inhibitor elenbecestat(2) were presented at the Alzheimer's Association International Conference (AAIC) held in Los Angeles, California, United States, from July 14 to 18, 2019 (Poster Presentation No.: P2-064).
BACE is a key enzyme in the production of Abeta peptides, which inhibits beta site of amyloid precursor protein (APP). BACE inhibitor may decrease the formation of toxic Abeta peptide aggregates in the brain, thereby thought to exert disease modifying effects and may have potential to slow the disease progression. On the other hand, in addition to APP, the other substrates with physiological role in synapse formation and function are known as a substance (substrate) changed by BACE.
At this time, the effect to Abeta level in CSF and synaptic damage were examined after 4 weeks of administration of BACE inhibitors using novel preclinical model mouse. For the examination compounds, elenbecestat (in-house discovery), verubecestat, and lanabecestat were used.
In addition, the effect to the synapse formation and function were evaluated by setting the numerous spinal densities on dendrite of brain cortex (number of spines per 10 micrometer of dendrites) and mitochondrial function (mitochondrial oxygen efficiency) of hippocampal synaptosomes (isolated presynaptic terminal) as an index. It is believed that decreases in spinal densities and mitochondrial function damage the synaptic function and deteriorate the cognitive function.
The dose of each BASE inhibitor was adjusted so as to be equivalent to the dose for clinical study in accordance with exploratory data of lowering effect of Abeta in mouse CSF. As a result, elenbecestat did not show significant effects on spinal density and mitochondrial function at dose of 3, 10mg/kg with significant decline of Abeta level in CSF (p
About Eisai
Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With approximately 10,000 employees working across our global network of R & D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including Neurology and Oncology.
Furthermore, we invest and participate in several partnership-based initiatives to improve access to medicines in developing and emerging countries.
For more information about Eisai Co., Ltd., please visit www.eisai.com
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