Future strategies of management of Alzheimer's Disease. The role of homotaurine.

Dementia and Alzheimer's Disease (AD) particularly will become in future one of the major problems that healthcare systems will have to face with in developed but also in developing countries, because of the progressive aging of the population and the age-associated increase in their incidence. There is a rapid increasing in life expectancy and in elderly percentage. Unfortunately, improvements in lifespan have not been matched by improvements in mental health span. In recent years, there has been a growing interest, supported by a large number of experimental, epidemiological and clinical studies, about the beneficial effects of some natural products in preventing various age-related pathologic conditions, including brain aging and neurodegeneration. Homotaurine, a small aminosulfonate substance that is present in different species of marine red algae, has been shown, in both in vitro and in vivo studies, to provide a relevant neuroprotective effect by its specific anti-amyloid activity and by its γ-aminobutyric acid type A receptor affinity. The name homotaurine was chosen because of its large homology with taurine (2 aminoethanesulfonate), which is one of the most abundant free amino acids in the brain. The two molecules share a very similar structure, but homotaurine contains one additional carbon. The therapeutic efficacy of homotaurine in AD has been investigated in three phase II, and in three Phase III clinical studies that did not reach their pre-defined primary endpoints. However, post-hoc analyses have shown positive and significant effects 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 APOE ε4 allele carriers, suggesting disease-modifying effects. Also in three post marketing (as supplement) studies in patients with Mild Cognitive Impairment (MCI) the results are very promising. In this review, we will present the pre-clinical and clinical evidence supporting the potential role of homotaurine as a promising candidate for both primary and secondary prevention of AD.