Homotaurine Induces Measurable Changes of Short Latency Afferent Inhibition in a Group of Mild Cognitive Impairment Individuals

Abstract

Current treatment options for patients with Alzheimer’s disease (AD) are limited at providing symptomatic relief, with no effects on the underlying pathophysiology. Recently, advances in the understanding of the AD pathogenesis highlighted the role of ABeta (Aβ) oligomers particularly interfering with mechanisms of cortical plasticity such as long-term potentiation (LTP) and long-term depression (LTD). These findings led to the development of potential anti-amyloid therapies, and among them homotaurine, a glycosaminoglycan mimetic designed to interfere with the actions of Aβ early in the cascade of amyloidogenic events, and by its γ-aminobutyric acid type (GABA) A receptor affinity. Recently, we showed that AD patients have impaired LTP-like cortical plasticity, as measured by standard theta burst stimulation protocols applied over the primary motor cortex (M1). Furthermore, AD patients have a weakened short latency afferent inhibition (SLAI), a neurophysiological measure of central cholinergic transmission, which changes reflect the cholinergic dysfunction occurring in the pathology. Here, we aimed at investigating whether homotaurine administration could modulate in vivo measured mechanisms of synaptic plasticity, namely LTP and LTD, and also SLAI in a group of mild cognitive impaired patients. We observed that homotaurine administration did not induce relevant changes of both LTP and LTD recordings, while induced changes of SLAI in our group of patients. We suggest that homotaurine effects are dependent on changes of cortical GABA transmission suggesting a potential role for this compound in ameliorating the cholinergic transmission by modulating the inhibitory cortical activity.

Homotaurine in Parkinson’s disease

“…We also report that PD patients in treatment with homotaurine significantly improved in UPDRS-I score and Epworth Scale score at the end of the study, while no differences in any of the assessment scales scores was revealed in the PD controls group. Moreover, patients in both groups showed no changes of performance in any neuropsychological test, and this is in line with previous studies, which failed to demonstrate an effect of homotaurine treatment on cognitive functions as measured by means of battery of neuropsychological tests in AD patients [5,29]. In detail, in the Alphase study, authors did not find significant change over 78 weeks in the neuropsychological variables (Alzheimer's Disease Assessment Scale-Cognitive Subscale and Clinical Dementia Rating-Sum of boxes), but they showed a trend toward greater decrease in volumetric MRI of the hippocampus [29].…”

“…Moreover, patients in both groups showed no changes of performance in any neuropsychological test, and this is in line with previous studies, which failed to demonstrate an effect of homotaurine treatment on cognitive functions as measured by means of battery of neuropsychological tests in AD patients [5,29]. In detail, in the Alphase study, authors did not find significant change over 78 weeks in the neuropsychological variables (Alzheimer's Disease Assessment Scale-Cognitive Subscale and Clinical Dementia Rating-Sum of boxes), but they showed a trend toward greater decrease in volumetric MRI of the hippocampus [29]. Authors suggested that changes in cognitive and neurobiological measures might not occur over the same time period and they might be considered as 25 …”

“…Authors showed that after 1 month of treatment, patients showed differences neither in neuropsychological performance nor in neurophysiological measures except for an effect on SAI measurements. This effect was interpreted as the result of high affinity binding of homotaurine for GABA-A receptors, which would consequently determine an action on cholinergic transmission by modulating the inhibitory cortical activity [29]. Taking this study into account, we could speculate that homotaurine might have a beneficial effect on vigilance by means of a modulatory action on the regulatory system of consciousness (sleep and awake), probably through its action on GABA-A receptors.…”

Comparative Oral Absorption of Different Citicoline and Homotaurine Formulations: A Single-Dose, Two-Period Crossover Trial in the Dog

“…Homotaurine (3-aminopropanesulfonate), an analogue of 4-aminobutyrate (γ-aminobutyric acid, GABA), is a small natural aminosulfonate compound identified in different species of marine red algae (Acrosorium uncinatum, Cladophora densa, Chondrus ocellatus, Gratelupia livida and Rhodymenia palmataa) and then chemically synthesized under the name of tramiprosate [10]. This substance may interfere with several cellular pathways and exert neuroprotective and neurotropic activities through different mechanisms including effects against the oxidative damage to DNA, antifibrillogenic activity, and antinociceptive and analgesic activities, related to the activation of GABA type-A receptors.…”

P4‐159: Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease

“…Therapeutic effects of taurine remain to be investigated in demented animal models with AD pathology. Considering the reevaluation of anti-amyloidogenic homotaurine for the potential role to ameliorate the cholinergic transmission in early AD, its analog compounds such as taurine are valuable therapeutic candidates for both cognitive enhancement and disease-modification (Figure 1) 27 . In this study, we examined both symptomatic and diseasemodifying effects of taurine in the demented adult APP/PS1 transgenic AD mouse model.…”