Use of serotonergic drugs to treat virus-induced thrombocytopenia

A technology for thrombocytopenia and serotonin, applied in the direction of drug combinations, blood diseases, antiviral agents, etc., can solve problems such as high burden

Pending Publication Date: 2020-11-03
NAT UNIV OF SINGAPORE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

High clinical and financial burden due to hospitalization required during severe infection

Method used

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  • Use of serotonergic drugs to treat virus-induced thrombocytopenia
  • Use of serotonergic drugs to treat virus-induced thrombocytopenia
  • Use of serotonergic drugs to treat virus-induced thrombocytopenia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Dengue infection induces platelet aggregation in mice

[0086] Wild-type (WT) mice were treated intraperitoneally (IP) with 10 6 DENV2 infection in plaque forming units (pfu). Blood was taken via cheek bleed 24 hours post-infection, spread on glass slides, stained with eosin and methylene blue, and viewed under a light microscope using a 10Ox magnification lens. Peripheral blood smears from infected mice revealed prominent platelet aggregation ( figure 1 ).

Embodiment 2

[0088] Mice lacking mast cells during dengue infection do not experience thrombocytopenia.

[0089] It has been previously shown that mast cell mediators contribute to plasma leakage during dengue infection [St John, A.L. et al., eLife 2, e00481 (2013); Syenina, A. et al., eLife 4, e05291 (2015)] . In this example, C57BL / 6 wild-type (WT) and mast cell-deficient (Sash) mice (on a C57BL / 6 background) were administered intraperitoneally (IP) with 10 6 DENV2 infection in plaque forming units (pfu). Blood was drawn via cheek bleed 24 hours post-infection, and platelet counts were measured using an automated hematology analyzer. Platelet counts of DENV-infected wild-type (WT) and mast cell-deficient (Sash) mice indicate that mice lacking mast cells (due to a point mutation in the promoter region of the ckit gene) do not experience thrombocytopenia during dengue infection syndrome, which occurred in control (WT) mice ( figure 2 ).

Embodiment 3

[0091] DENV2-activated mast cells induce platelet activation

[0092] Further in vitro studies were performed to determine whether mast cell products could directly activate platelets. Mouse bone marrow-derived mast cells (MCs) were incubated with DENV2 for 2 hours. The degranulation product was isolated and used to stimulate mouse whole blood. After 15 minutes, the samples were fixed with 4% paraformaldehyde for 2 hours at 4 degrees. Samples were then washed and stained for the platelet marker CD41 and the activation marker CD62P and analyzed by flow cytometry. As can be seen, DENV2 alone and unstimulated mast cells did not result in significant levels of platelet activation. However, DENV2-activated mast cells release mediators that lead to platelet activation ( image 3 ).

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Abstract

The present invention relates to the use of serotonergic compounds for the treatment of virus-induced thrombocytopenia. More particularly, the invention relates to methods of treating thrombocytopeniaby blocking serotonin activity. For example, inhibitors of receptor 5HT2A and / or receptor 5HT1A and / or inhibitors of mast cell degranulation and / or inhibitors of serotonin uptake may be used. Preferably, the thrombocytopenia is induced by dengue or Japanese Encephalitis virus, and the inhibitors are preferably ketanserin, WAY-100135, sarpogrelate, or fluoxetine.

Description

technical field [0001] The present invention relates to the treatment of virus-induced thrombocytopenia. More particularly, the invention relates to methods of treating thrombocytopenia by blocking serotonin activity. For example, inhibitors of receptor 5HT2A and / or receptor 5HT1A and / or inhibitors of mast cell degranulation and / or inhibitors of serotonin uptake may be used. Background technique [0002] Dengue fever is caused by infection with the dengue virus, which has four serotypes. There are no targeted therapies available to treat dengue infection or its characteristic symptoms such as thrombocytopenia or bleeding. Current measures involve symptomatic treatment as well as vaccination. Some communities, such as Singapore, engage in vector control to prevent further spread of the disease [Guzman, M.G. & Harris, E. Dengue. The Lancet 385, 453-465 (2015)], but the results of vector control have been limited. Although dengue usually resolves on its own, there is a poss...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61P7/04A61K31/517A61K31/495A61K31/225A61K31/138
CPCA61K31/138A61K31/225A61K31/495A61K31/517A61P7/04A61K31/519A61K31/554A61K31/404A61K31/352A61K31/4535Y02A50/30A61P31/14A61K31/343A61K31/4525A61K31/497
Inventor A·L·圣约翰M·F·B·马斯里A·拉肖尔
Owner NAT UNIV OF SINGAPORE
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