Rui Seabra Ferreira, Daniel Carvalho Pimenta, Ricardo de Oliveira Orsi, Silvia Regina S. Barraviera, Luciana Patrícia F. Abbade, Alexandre Naime Barbosa, Luis Eduardo Ribeiro da Cunha, Benedito Barraviera
Center for the Study of Venoms and Venomous Animals (CEVAP), UNESP – Univ Estadual Paulista, Botucatu/SP, Brazil
To bridge the GAP between basic and applied sciences is needed to push forward disease research and therapeutics. What types of drug leads are truly “druggable”, sit in “patented bioproducts space” and can be pushed towards clinical trials? We present two successful translational cases of bioproducts from laboratory bench to the bedside.
Case 1: Fibrin sealant derived from snake venom (FSSV). This product is composed of a serine protease (thrombin-like enzyme) derived from South American rattlesnake (Crotalus durissus terrificus) venom and cryoprecipitate of buffaloes (Bubalus bubalis) rich in fibrinogen. The activity of snake venom serine protease is 1,500-fold more potent than that of human thrombin employed in commercial sealants. The cryoprecipitate replaces human hemoderivatives, which makes the production more affordable and eliminates the possibility of infectious disease transmission. FSSV is a bioproduct of animal origin produced at the Center for the Study of Venoms and Venomous Animals (CEVAP) of UNESP, Brazil, to treat chronic venous ulcers of 240 patients of a phase II/III multicenter clinical trial. The phase I/II clinical trial with ten pacients was carried out and there was complete healing in 38.8% of the ulcers. There was decrease of their area with wound bed preparation in 33.3%, therefore a significant improvement in 72.1% of the cases was observed in only three months of treatment. Based on such results, the product was considered a safe candidate and clinically promising. In addition, FSSV is being successfully tested in vitro and in vivo for its use as a three-dimensional scaffold for stem cells, since it is biodegradable and maintains the cells viable at the application site.
Case 2: Africanized honeybee antivenom (AHBA). In Brazil, Africanized honeybees provoke more than 10 thousand envenomations and approximately 40 deaths per year. Since it is an issue limited to the American continent that had no specific treatment, a new antivenom to treat multiple stings was developed. One of the major challenges was the standardization of the product, because of the antigenic characteristics of the venom. The antivenom was developed at CEVAP and produced by the Vital Brazil Institute (IVB) based on horse hyperimmunization with the main toxic fractions of the venom. Each milliliter of AHBA neutralizes 1.25 mg of venom and 10 mL of antivenom can treat about 100 stings. AHBA is being tested in a phase I/II multicenter clinical trial with 20 participants. Its delivery route is intravenous and the administration follows a strict clinical protocol that aims to rapidly neutralize and eliminate the venom toxic effects.
Both products were patented and by the end of the clinical trials, they will be available in the Brazilian public health system (SUS). They will aid the treatment of chronic venous ulcer patients and multiple Africanized Honeybee sting victims, two major neglected issues. The involved team of researchers acquired the required expertise to develop new drugs through translational research by applying modern biotechnological tools and aiming at solving health problems with regional bioproducts.
Keywords: Clinical trials, Bioproducts, Translational research.