Heterologous fibrin sealant derived from snake venom: from bench to bedside – an overview

 

Rui Seabra Ferreira Jr^1 2 4, Luciana Curtolo de Barros², Luciana Patrícia Fernandes Abbade³, Silvia Regina Catharino Sartori Barraviera³, Maria Regina Cavariani Silvares³, Leticia Gomes de Pontes^1  2, Lucilene Delazari dos Santos^1  2, Benedito Barraviera^1  2 

 

1 Graduate Program in Tropical Diseases, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP, Brazil.

2 Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP, Brazil.

3 Department of Dermatology and Radiology, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, SP, Brazil.

4 CEVAP/ UNESP, Avenida José Barbosa de Barros, 1780, Botucatu, SP CEP 18610-307, Brazil.

 

ABSTRACT

Hemostatic and adhesive agents date back to World War II, when homologous fibrin sealant came onto scene. Considering that infectious diseases can be transmitted via human blood, a new heterologous fibrin sealant was standardized in the 1990s. Its components were a serine protease (a thrombin-like enzyme) extracted from the venom of Crotalus durissus terrificus snakes and a fibrinogen-rich cryoprecipitate extracted from the blood of Bubalus bubalis buffaloes. This new bioproduct has been used as a coagulant, sealant, adhesive and recently as a candidate scaffold for mesenchymal stem cells and bone and cartilage repair. This review discusses the composition of a new heterologous fibrin sealant, and cites published articles related to its preclinical applications aiming at repairing nervous system traumas and regenerating bone marrow. Finally, we present an innovative safety trial I/II that found the product to be a safe and clinically promising candidate for treating chronic venous ulcers. A multicenter clinical trial, phase II/III, with a larger number of participants will be performed to prove the efficacy of an innovative biopharmaceutical product derived from animal venom.

 

Key words: Fibrin sealant; Snake venom; Cryoprecipitate coagulum; Thrombin-like enzyme; Buffaloes

 

Funding

This study was supported by the São Paulo Research Foundation (FAPESP) (process no. 2009/53846-9 granted to BB and RSF Jr; process no. 2012/08101-8 granted to RSF Jr and process no. 2014/13299-7 granted to LDS), and to the National Council for Scientific and Technological Development (CNPq) (process no. 563582/2010-3 granted to BB). This work was also supported by the Coordination for the Improvement of Higher Education Personnel (CAPES) through Edital Toxinologia CAPES no. 063/2010, process no. 230.38.006285/2011-21, AUXPE Toxinologia 1219/2011 and by the Department of Science and Technology (DECIT) and the Secretariat of Science, Technology and Strategic Inputs (SCTIE), CNPq process n. 401170/2013-6, of the Brazilian Ministry of Health. RSF Jr is a CNPq DTI research fellow (310395/2014-3).

 

Received: January 14, 2017.

Revised: March 16, 2017.

Accepted: April 4, 2017.

 

Correspondence: rseabra@cevap.unesp.br

 

Authors’ contributions

RSF Jr., LCB, SRCSB, MRCS, LDS and LGP searched the databases (PubMed, Scopus, Scielo and Web of Science) and wrote the review. RSF Jr., LPFA and BB corrected the manuscript and prepared the images. All authors read and approved the final manuscript.

 

Competing interests

One of the authors of this article, Dr. Benedito Barraviera, is the Editor-in-Chief of Journal of Venomous Animals and Toxins including Tropical Diseases. He did not get involved in the peer review process of this manuscript.

 

Consent for publication

Written informed consent was obtained from the patients for publication of this study.

 

Ethics approval and consent to participate

Part of the research herein presented was approved by the Research Ethics Committee of the Botucatu Medical School (CEP protocol n. 501.232). Moreover, the clinical trials described in the section “The human use of heterologous fibrin sealant” were approved by the National Commission for Ethics on Research (CONEP) and received the Certificate of Presentation for Ethical Appreciation (CAAE) - 19006813.4.1001.5411.

 

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