Use of Serotonergic Drugs to Treat Virus-Induced Thrombocytopenia
PATENT STATUS
PCT application disclosing this invention was filed in October 2018.
OVERVIEW OF TECHNOLOGY ON OFFER
Novel molecular targets for treatment of dengue and other virus-induced thrombocytopenia.
BRIEF DESCRIPTION
Dengue fever is caused by infection with dengue virus, and there are no targeted therapies available to treat dengue infection or its characteristic symptoms such as thrombocytopenia or haemorrhage. Although dengue fever may resolve on its own, there is a possibility of severe complications such as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), wherein patients experience substantially decreased platelet counts, abdominal pain and plasma leakage that can lead to organ damage and/or shock. DHF/DSS patients need to be hospitalised and this is a high burden both clinically and economically. Therefore, any treatment for dengue symptoms would represent a significant benefit for both patients and healthcare providers.
Thrombocytopenia, a hallmark feature of many viral infections such as dengue, Japanese Encephalomyelitis Virus (JEV), Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), filovirus, bunyavirus etc., is a drastic reduction in circulating platelet counts which can predispose a patient to severe bleeding and can be fatal. Thrombocytopenia frequently occurs in both mild and severe forms of dengue, and is a constant finding in DHF/DSS. There are currently no targeted therapies to treat dengue-induced thrombocytopenia since the underlying molecular mechanisms are unknown.
Dr. Ashley St. John’s lab at Duke-NUS Medical School has identified that by targeting serotonin release and uptake in mast cells and platelets, thrombocytopenia can be treated in animals infected with dengue virus and JEV. Mice infected with dengue virus (DENV2) showed platelet activation and aggregation. Upon blocking the serotonin receptors with antagonists against either the 5HT2A receptor or 5HT1A receptor in these dengue-infected mice, circulating platelet numbers were restored to normal levels. Further, dengue-infected mice treated with a selective serotonin reuptake inhibitor (SSRI) showed restoration of platelet numbers to normal levels. A similar effect was observed in mice infected with JEV upon administering a 5HT2A antagonist. Our findings highlight that targeting serotonin, a host factor, can ameliorate thrombocytopenia, revealing a potential therapeutic target of disease. Targeting of host factors has the added benefit of avoiding the potential of virus adaptation. Notably, other infections caused by haemorrhagic fever viruses, such as filoviruses and bunyaviruses, also induce thrombocytopenia and may be responsive to this therapeutic strategy.
POTENTIAL APPLICATIONS
Treatment of dengue and other virus-induced thrombocytopenia.
KEY BENEFIT
Novel approach to treatment of dengue and virus-induced thrombocytopenia by targeting a host factor, serotonin.
PUBLICATIONS
Masri, Mohamad Fadhli Bin, Chinmay Kumar Mantri, Abhay PS Rathore, and Ashley L. St John. "Peripheral serotonin causes dengue-induced thrombocytopenia through 5HT2 receptors." Blood (2019): blood-2018.
INVENTOR BIO
Ashley Lauren St. John
CONTACT
Please email us for further enquiries: cted@duke-nus.edu.sg