title: The potential protective effect of tramiprosate (homotaurine) against Alzheimer's disease: a review.
abstract: Due to the progressive aging of the population and to the age-associated increase in its incidence, Alzheimer's disease (AD) will become in near future one of the major challenges that healthcare systems will have to face with in developed countries. Since the pathophysiological process of AD is thought to begin many years before the clinical diagnosis of dementia, in theory there is an opportunity for preventive therapeutic interventions. In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, in the beneficial effects of some natural compounds in preventing various age-related pathologic conditions, including brain aging and neurodegeneration. Homotaurine, a small aminosulfonate compound that is present in different species of marine red algae, has been shown, in both in vitro and in vivo models, to provide a relevant neuroprotective effect by its specific anti- amyloid activity and by its γ-aminobutyric acid type A receptor affinity. The therapeutic efficacy of homotaurine in AD has been investigated in a pivotal Phase III clinical study that did not reach its pre-defined primary endpoints. However, post-hoc analyses have shown positive and significant effects of homotaurine on secondary endpoints and subgroups of patients, including a reduction in hippocampal volume loss and lower decline in memory function in the overall cohort, as well as a reduction in global cognitive decline in APOE4 allele carriers, suggesting a disease-modifying effects. In this review, we will examine the pre-clinical and clinical evidence supporting the potential role of homotaurine as a promising candidate for both primary and secondary prevention of AD.
authors.affiliation: University of Roma Tor Vergata, and Scientific Director, IRCSS Santa Lucia Foundation, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrannini
authors.forename: Niccolò
authors.initials: N
authors.lastname: Marchionni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scapagnini
authors.forename: Marco
authors.initials: M
authors.lastname: Trabucchi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D018697:Nootropic Agents / Q000494:pharmacology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C054369:MAPT protein, human; D018697:Nootropic Agents; D016875:tau Proteins; D013654:Taurine; C001355:tramiprosate