A Review on Tramiprosate (Homotaurine) in Alzheimer's Disease and Other Neurocognitive Disorders

Manzano, Sagrario; Agüera, L.; Aguilar, Miquel; Olazarán, Javier

doi:10.3389/fneur.2020.00614

Cited by 54 publications

(42 citation statements)

References 79 publications

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“…The amyloid-β oligomers are believed to be a key pathogenic driver in the disease process. The homotaurine mechanism prevents the self-assembly of misfolded proteins into amyloid-β oligomers that leads to amyloid aggregation and subsequently causes neurotoxicity and clinical progression of AD [ 137 ]. This genetic knowledge emerged after phase III clinical studies of tramiprosate in AD patients and prompted a precision medicine approach and analysis of the genetically defined subset of AD patients in homotaurine studies.…”

Section: Marine Compounds Against Alzheimer’s Disease: From Sea To Cellsmentioning

confidence: 99%

Exploitation of Marine Molecules to Manage Alzheimer’s Disease

2021

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Neurodegenerative diseases are sociosanitary challenges of today, as a result of increased average life expectancy, with Alzheimer’s disease being one of the most prevalent. This pathology is characterized by brain impairment linked to a neurodegenerative process culminating in cognitive decline and behavioral disorders. Though the etiology of this pathology is still unknown, it is usually associated with the appearance of senile plaques and neurofibrillary tangles. The most used prophylaxis relies on anticholinesterase drugs and NMDA receptor antagonists, whose main action is to relieve symptoms and not to treat or prevent the disease. Currently, the scientific community is gathering efforts to disclose new natural compounds effective against Alzheimer’s disease and other neurodegenerative pathologies. Marine natural products have been shown to be promising candidates, and some have been proven to exert a high neuroprotection effect, constituting a large reservoir of potential drugs and nutraceutical agents. The present article attempts to describe the processes of extraction and isolation of bioactive compounds derived from sponges, algae, marine bacteria, invertebrates, crustaceans, and tunicates as drug candidates against AD, with a focus on the success of pharmacological activity in the process of finding new and effective drug compounds.

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Section: Marine Compounds Against Alzheimer’s Disease: From Sea To Cellsmentioning

confidence: 99%

Exploitation of Marine Molecules to Manage Alzheimer’s Disease

2021

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“…Studies on model mice showed that long-term administration of carnosine affected the suppression of the accumulation of senile plaques [ 27 ], and it also had protective and anti-inflammatory effects on brain cells [ 28 ]. A similar low-molecular-weight prodrug is a homotaurine [ 101 ]. Homotaurine was also shown to eliminate senile plaques and to have pharmacokinetics that could pass through the BBB, and a large-scale phase 3 study was conducted in humans.…”

Section: Discussionmentioning

confidence: 99%

Influence of Imidazole-Dipeptides on Cognitive Status and Preservation in Elders: A Narrative Review

Masuoka

Lei

et al. 2021

Nutrients

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The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer’s disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food ingredients has been widely conducted. In particular, histidine-containing dipeptides, also known as imidazole dipeptides derived from meat, have received much attention. Imidazole dipeptides are abundant in meats such as poultry, fish, and pork. As evidenced by data from recent human intervention trials conducted worldwide, daily supplementation of carnosine and anserine, which are both imidazole dipeptides, can improve memory loss in the elderly and reduce the risk of developing AD. This article also summarizes the latest researches on the biochemical properties of imidazole dipeptides and their effects on animal models associated with age-related cognitive decline. In this review, we focus on the results of human intervention studies using supplements of poultry-derived imidazole dipeptides, including anserine and carnosine, affecting the preservation of cognitive function in the elderly, and discuss how imidazole dipeptides act in the brain to prevent age-related cognitive decline and the onset of dementia.

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“…Potent inhibitors of the formation of Abeta fibrils or plaques are therapeutic antibodies, as described below. A small molecule that blocks the formation of Abeta dimers is homotaurine (tramiprosate) [ 83 ], which is a highly polar molecule, 3-amino-1-propanesulfonic acid, that, in the absence of carrier mediated transport, would be expected to have minimal BBB transport. A clinical trial of homotaurine for AD did not result in an improvement in cognitive decline [ 84 ].…”

Section: Small Molecule Drugs For Alzheimer’s Diseasementioning

confidence: 99%

Treatment of Alzheimer’s Disease and Blood–Brain Barrier Drug Delivery

Pardridge

2020

Pharmaceuticals

114

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Despite the enormity of the societal and health burdens caused by Alzheimer’s disease (AD), there have been no FDA approvals for new therapeutics for AD since 2003. This profound lack of progress in treatment of AD is due to dual problems, both related to the blood–brain barrier (BBB). First, 98% of small molecule drugs do not cross the BBB, and ~100% of biologic drugs do not cross the BBB, so BBB drug delivery technology is needed in AD drug development. Second, the pharmaceutical industry has not developed BBB drug delivery technology, which would enable industry to invent new therapeutics for AD that actually penetrate into brain parenchyma from blood. In 2020, less than 1% of all AD drug development projects use a BBB drug delivery technology. The pathogenesis of AD involves chronic neuro-inflammation, the progressive deposition of insoluble amyloid-beta or tau aggregates, and neural degeneration. New drugs that both attack these multiple sites in AD, and that have been coupled with BBB drug delivery technology, can lead to new and effective treatments of this serious disorder.

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A Review on Tramiprosate (Homotaurine) in Alzheimer's Disease and Other Neurocognitive Disorders

Cited by 54 publications

References 79 publications

Exploitation of Marine Molecules to Manage Alzheimer’s Disease

Exploitation of Marine Molecules to Manage Alzheimer’s Disease

Influence of Imidazole-Dipeptides on Cognitive Status and Preservation in Elders: A Narrative Review

Treatment of Alzheimer’s Disease and Blood–Brain Barrier Drug Delivery

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