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P2‐456: NPT001: A candidate therapeutic for clearance of β‐amyloid and tau aggregates in Alzheimer's disease
Author(s) -
Fisher Richard,
Gan Kimberley,
Krishnan Rajaraman,
Tsubery Haim,
Masliah Eliezer,
Rockenstein Edward,
Kirschner Daniel,
Inouye Hideyo,
Myszka David,
Cirrito John,
Green Kim,
Wright Jason,
Solomon Jonathan,
LaFerla Frank,
Solomon Beka
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1328
Subject(s) - genetically modified mouse , chemistry , amyloid (mycology) , biophysics , fibril , amyloid beta , tau protein , transgene , protein aggregation , extracellular , alzheimer's disease , pharmacology , pathology , neuroscience , biochemistry , medicine , peptide , biology , disease , gene
ture as well as in AD model mice. The activation of the alpha-secretase in consequence enhanced non-amyloidogenic processing of APP and attenuated A-beta formation. Results: Recently, we set up a clinical trial to prove this therapeutic concept in human Alzheimer’s disease patients and now provide first data. The multicenter randomized placebo-controlled parallel-group study aims to demonstrate an enhancement of the alpha-secretase activity as measured by alteration of APPs-alpha levels in the cerebrospinal fluid under 30 days period Acitretin therapy in patients with mild to moderate AD. Expression of the alpha-secretase ADAM10 itself is monitored in the periphery (platelets) to evaluate changes in gene expression. The safety and tolerability of Acitretin in AD patients is proven by general clinical parameters. In addition, the pro-inflammatory marker interleukin 4 and the anti-inflammatory marker interleukin 6 will be determined by ELISA. Conclusions: The study in human patients will be the first to qualify Acitretin as a potential Alzheimer disease-modifying substance. If reduction of APPs-alpha in the cerebrospinal fluid occurs and ADAM10 is up regulated in peripheral blood cells, this will provide insight into the mechanistic context before larger and long-lasting studies with retinoids in Alzheimer’s disease patients will be ensued.