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Pharmaceutical compositions comprising a tungsten salt (VI) for the treatment of neurodegenerative disorders, particularly alzheimer's disease and schizophrenia

一种神经退行性、障碍的技术，应用在精神分裂症领域，能够解决神经退行性障碍精神分裂治疗和/或预防不能令人满意等问题，达到低价格的效果

Inactive Publication Date: 2011-07-13
UNIV DE BARCELONA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Despite all the research efforts invested in the past, the treatment and / or prevention of neurodegenerative disorders such as Alzheimer's disease or schizophrenia is still far from satisfactory

Method used

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  • Pharmaceutical compositions comprising a tungsten salt (VI) for the treatment of neurodegenerative disorders, particularly alzheimer's disease and schizophrenia
  • Pharmaceutical compositions comprising a tungsten salt (VI) for the treatment of neurodegenerative disorders, particularly alzheimer's disease and schizophrenia
  • Pharmaceutical compositions comprising a tungsten salt (VI) for the treatment of neurodegenerative disorders, particularly alzheimer's disease and schizophrenia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1: Effect of Tungstate on Ser-9 Phosphorylation of GSK3-β in Neuroblastoma Cell Line SH-SY5

[0034] To investigate whether tungstate affects neuronal cells, the effect of sodium tungstate dihydrate on GSK3-β in the neuroblastoma cell line sH-SY5Y (ref: 94030304 of the European Collection of Cell Cultures, Salysbury, Whitshire, Great Britain) was analyzed Effects of Inhibition of Ser-9 Phosphorylation. Human neuroblastoma SH-SY5Y cells were grown in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (FBs; Invitrogen-Gibco), 2 mM glutamine, and 50 μg / ml gentamicin. ; Invitrogen-Gibco, Carlsbad, CA). The day before the experiment, cells were plated in multi-well plates with NeuroBasal (NB) serum-free medium (Invitrogen-Gibco). Sodium tungstate dihydrate was dissolved in double distilled water and added to the incubation medium at a final concentration of 0.1, 1 or 5 mM, and the cells were incubated for 5 or 10 minutes. Control cell...

Embodiment 2

[0037] Example 2: Effect of sodium tungstate on tau phosphorylation in vivo

[0038] To study the effect of tungstate on tau phosphorylation in vivo, the phosphorylation degree of this protein and the phosphorylation degree of GSK3-β at Ser-9 in untreated and tungstate-treated healthy Wistar rat brains were first analyzed. Male Wistar rats (IFFA CREDO, L'Arbresse, France) weighing 220-240 g were housed one cage per animal on a 12:12-hour light-dark cycle under controlled temperature and humidity. No significant changes in tau or GSK3 phosphorylation were observed in either group in the presence or absence of tungstate ( figure 2 A). These results are consistent with previous data showing that tungstate was inactive when tested in healthy animals.

[0039] The effect of tungstate was then tested in a model of insulin resistance where tungstate is pharmaceutically active: obese rats induced by a fat-rich diet. The rats were fed either a controlled diet (8% of calories as fat...

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Abstract

Pharmaceutical compositions comprising an effective amount of a tungsten (VI) compound, preferably of a tungstate salt, and more preferably of sodium tungstate (Na2WO4 ), are useful for the prophylactic and / or therapeutical treatment of neurodegenerative disorders in a mammal, including a human, in particular, for the prophylactic and / or therapeutical treatment of Alzheimer's disease or schizophrenia. The effect of sodium tungstate dihydrate on the phosphorylation of tau in a model of rat insulin resistance and in a model of type-1 diabetes has been assessed. The therapeutic treatment of tauopathies that derives from this invention involves several advantages: it targets a GSK3; specificity since it reduces the abnormal hyperphosphorylation of a neural specific protein, tau, efficacy, lack of toxicity, and low price.

Description

technical field [0001] The present invention relates to the use of pharmaceutical compositions comprising tungsten(VI) compounds for the treatment of neurodegenerative disorders, in particular Alzheimer's disease and other microtubule-associated diseases (i.e. involving deposition of abnormal microtubule-associated protein isoforms in the brain neurodegenerative disorders), and schizophrenia. Background technique [0002] Neurodegenerative disorders can be defined as chronic and progressive disorders of the nervous system affecting neurological and behavioral function, beginning with specific biochemical changes that culminate in distinct histopathological and clinical syndromes. Among these disorders are Alzheimer's disease, Huntington's disease and Parkinson's disease. [0003] Alzheimer's disease, the most common form of dementia in older adults, involves the parts of the brain that control thought, memory and language. It is characterized by two main pathological marke...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K33/24A61P25/18A61P25/28
CPCA61K33/24A61P25/00A61P25/14A61P25/16A61P25/18A61P25/28
Inventor J·J·奎诺瓦特希瑞拉J·埃维拉德格拉多J·道明奎兹雷耶斯R·格密斯德芭芭拉A·格默兹拉默斯D·扎夫拉洛佩兹H·克罗米诺拉欧卡纳
Owner UNIV DE BARCELONA
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