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    Non-anticoagulant heparin as a pre-exposure prophylaxis prevents Lyme disease infection

    Author
    Lin, Yi Pin; Yu, Yanlei; Marcinkiewicz, Ashley L.; Lederman, Patricia; Hart, Thomas M.; Zhang, Fuming; Linhardt, Robert J.
    ORCID
    https://orcid.org/0000-0003-2219-5833
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    NON-ANTICOAGULANT HEPARIN AS A PRE-EXPOSURE PROPHYLAXISNON-ANTICOAGULANT HEPARIN AS A PRE-EXPOSURE PROPHYLAXIS.pdf (655.2Kb)
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    Date Issued
    2020-03-13
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    Full Citation
    Non-anticoagulant heparin as a pre-exposure prophylaxis prevents Lyme disease infection, Y.-P. Lin, , Y. Yu, A. Marcinkiewicz, P. Lederman, T. Hart, F. Zhang, R. J. Linhardt, ACS Infectious Diseases,6, 503−514, 2020.
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    URI
    https://hdl.handle.net/20.500.13015/5396; https://doi.org/10.1021/acsinfecdis.9b00425
    Abstract
    Lyme disease (LD) is caused by the spirochete Borrelia burgdorferi sensu lato (Bbsl). After transmission to humans by ticks, Bbsl spreads to multiple organs, leading to arthritis, carditis, and neuroborreliosis. No effective prophylaxis against human LD prior to tick exposure is currently available. Thus, a pre-exposure prophylaxis (PrEP) against LD is needed. The establishment of LD bacteria at diverse sites is dictated partly by the binding of Bbsl to proteoglycans (PGs) and glycosaminoglycans (GAGs) in tissues. The drug heparin is structurally similar to these GAGs and inhibits Bbsl attachment to PGs, GAGs, cells, and tissues, suggesting its potential to prevent LD. However, the anticoagulant activity of heparin often results in hemorrhage, hampering the development of this compound as LD PrEP. We have previously synthesized a non-anticoagulant version of heparin (NACH), which was verified for safety in mice and humans. Here, we showed that NACH blocks Bbsl attachment to PGs, GAGs, and mammalian cells. We also found that treating mice with NACH prior to the exposure of ticks carrying Bbsl followed by continuous administration of this compound prevents tissue colonization by Bbsl. Furthermore, NACH-treated mice develop greater levels of IgG and IgM against Bbsl at early stages of infection, suggesting that the upregulation of antibody immune responses may be one of the mechanisms for NACH-mediated LD prevention. This is one of the first studies examining the ability of a heparin-based compound to prevent LD prior to tick exposure. The information presented might also be extended to prevent other infectious diseases agents.;
    Description
    ACS Infectious Diseases, 6, 503−514; Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Publisher
    American Chemical Society (ACS)
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; ACS Infectious Diseases; https://harc.rpi.edu/;
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    A full text version is available in DSpace@RPI;
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