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[P‐190]: AB derivatives as potentially safer vaccines for Alzheimer's disease
Author(s) -
Asuni Ayodeji,
Mestre-Frances Nadine,
Verdier Jean-Michel,
Knudsen Elin,
Trouche Stephanie,
Scholtzova Henrieta,
Quartermain David,
Frangione Blas,
Wisniewski Thomas,
Sigurdsson Einar M.
Publication year - 2005
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.2005.06.249
Subject(s) - lemur , vaccination , medicine , adjuvant , immune system , immunology , immunization , antibody , titer , alzheimer's disease , antibody titer , disease , biology , primate , neuroscience
based on an extensive preclinical literature which shows that AL-108 has potent neuroprotective, memory enhancing and neurotrophic properties. Furthermore, the data from these studies provide insights into a proposed mechanism of action of AL-108 against two primary pathologies of AD beta amyloid toxicity and microtubule breakdown that is associated with tau hyperphosphorylation. Objectives: To evaluate AL-108 in preclinical and toxicological studies toward clinical trials in Alzheimer’s disease patients. Methods and Results: Neuroprotective activities of AL-108 have been investigated in vitro against: The AD toxin ( amyloid peptide); The toxic envelope protein of the human immunodeficiency virus (HIV; gp120); Glucose deprivation; Electrical blockade (tetrodotoxin); Oxidative stress (hydrogen peroxide and glutathione); Dopamine toxicity and excitotoxicity (N-methyl-D-aspartate). AL-108 has also been evaluated as a potential neuroprotectant in a variety of animal models related to AD: The rat cholinotoxicity model; Apolipoprotein E-deficient mice; Mouse head trauma model; Hypertensive rat stroke model. AL-108 is an eight amino acid peptide with the following characteristics: It has a lipophilic structure that allows penetration through lipid membranes as in the case of the cellular membrane and the blood brain barrier; It has intrinsic sheet breaker characteristics, thus acting as a peptide chaperone to protect against toxic A plaque associated with AD; It chelates trace amounts of heavy metals, thus preventing toxicity; It binds to tubulin and promotes proper microtubule assembly as a peptide chaperone. In conclusion, based on the preclinical results toxicology studies have been peroformed. Good Laboratory Practice (GLP) animal studies have demonstrated that AL-108 is safely tolerated, brain bioavailable by intranasal, intravenous and subcutaneous routes and suitable for drug development. Allon Therapeutics has filed an Investigational New Drug application with the United States Food and Drug Administration for AL-108 and has received FDA approval to proceed.