Addressing Alzheimer's disease tangles: from NAP to AL-108.
AL-108 is the intranasal formulation of NAP (a peptide of eight amino acids, NAPVSIPQ). Phase IIa clinical results have recently shown that AL-108 has a positive impact on memory function in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease (AD). The clinical development of AL-108 has been based on extensive studies showing pre-clinical efficacy for NAP. NAP has demonstrated potent neuroprotective activity in vitro and in vivo. Its mechanism of action is thought to center on the modulation of microtubule stability in the face of outside damage. Such an effect on structures of such central importance in a broad range of cellular functions is thought to explain NAP's activity in wide ranging models of cellular damage and neurodegeneration. The following article reviews NAP's discovery and pharmacological characterization that has led to clinical development of a novel tangle-directed drug candidate.
Gozes
Illana
I
The Adams Super Center for Brain Studies, The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, Levi-Edersheim-Gitter Institute for Functional Brain Imaging, The Elton Laboratory for Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. igozes@post.tau.ac.il
Stewart
Alistair
A
Morimoto
Bruce
B
Fox
Anthony
A
Sutherland
Karole
K
Schmeche
Donald
D
D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage*; D016875:tau Proteins / Q000378:metabolism
C117632:Adnp protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D016875:tau Proteins; C425904:davunetide