| Grant number: | 20/01107-7 |
| Support Opportunities: | Regular Research Grants |
| Start date: | July 01, 2021 |
| End date: | December 31, 2023 |
| Field of knowledge: | Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology |
| Principal Investigator: | Mirian Akemi Furuie Hayashi |
| Grantee: | Mirian Akemi Furuie Hayashi |
| Host Institution: | Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil |
| Associated researchers: | Claudiana Lameu ; Fabio Cardoso Cruz ; Marcelo Alves da Silva Mori ; Marcelo Tatit Sapienza ; Vitor Marcelo Silveira Bueno Brandão de Oliveira |
Abstract
Toxins from animal venom are a material of great scientific interest, mainly due to their possible use for therapeutic purposes, which includes their use as drugs and/or as structural model for the development of drugs with therapeutic potential for the treatment of human diseases, in addition to their possible application as tools for biotechnological purposes. Crotamine, which is one of the most abundant toxins in the rattlesnake venom, is capable of penetrating cells, in addition to transporting DNA molecules into cells with special specificity for proliferating cells. In the last years, our group has demonstrated the importance of proteoglycans in crotamine internalization processes, for the specificity of this native polypeptide by dividing cells and in selective cytotoxic activity. The study on the viability of using the synthetic and/or modified analogs of native crotamine, as well as the expression of recombinant crotamine or synthetic form as alternative sources of obtaining this compound, suggested in 2013 that the purification of native crotamine from the collected venom of rattlesnakes kept in captivity would still be the most economically feaseble. However, aiming at the development of a plan for the use as a therapeutics of crotamine obtained under GMP conditions for use in humans, it led us to reconsider and invest in the generation of the analog by chemical synthesis. Alternative routes of administration, new formulations (nanoparticles) and possible adverse effects will be evaluated in the present study, including with regard to their use in the effects on animal metabolism, and in the therapy of cancer and renal disorders. The use of crotamine for renal disease therapy was recently suggested by our group, remembering that this is the organ with the highest accumulation of this polypeptide in vivo and that there are no therapies available for the renal region targeted by the accumulation of crotamine, with no apparent toxic effect at concentrations used for therapeutic purposes. Therefore, we hope to validate the real feasibility of using the synthetic analogue of crotamine for the therapy of patients with renal or metabolic diseases, or those with tumor. (AU)
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