A protein discovered in native Brazilian spiders that live in São Paulo State could save the Tasmanian devil (Sarcophilus harrisii), a species of marsupial endemic to the island off Australia’s south coast. Known to the world through Taz, a character in Looney Tunes cartoons, the species is being devastated by devil facial tumor disease (DFTD), a highly contagious form of cancer that disfigures the snout and mouth, preventing the animal from feeding.
“I’m very happy that a molecule discovered during my PhD research could save a species from extinction. Since 2000, when I presented the research, we’ve known gomesin is a powerful molecule with significant bactericidal, antifungal and antiviral activity, but I could never have imagined it would have the potential to prevent the disappearance of a species,” said Pedro Ismael da Silva Jr., a scientist affiliated with the Center for Research on Toxins, Immune Response & Cell Signaling (CeTICS), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP.
The discovery of gomesin was no accident. During his PhD research at the University of São Paulo’s Biomedical Science Institute (ICB–USP), where he defended his thesis in 2000, Silva looked for bioactive molecules in the blood of spiders.
“Venomous animals have long been a source of new molecules for drug development,” Silva told Agência FAPESP. “There’s a lot of interest in spiders, mainly because they’re very ancient animals that have been on Earth for 450 million years and haven’t changed much. Also, they can survive in contaminated environments and must have a mechanism that defends them against that kind of threat.”
One of the molecules discovered by Silva was gomesin, a protein found in the blood of the São Paulo black tarantula Acanthoscurria gomesiana. “In recent years, our lab has found some 30 promising molecules, including gomesin. They’re currently being evaluated,” he said.
What makes gomesin interesting for cancer treatment is its ability to inhibit cell development. “It acts on the cellular cycle, modifying and hindering the development of tumor cells, which typically propagate rapidly. Therefore, it could be used against any kind of cancer,” Silva explained.
In the case of bacteria and fungi, gomesin acts on the cell membrane. “In these microorganisms, the cell membrane is usually negatively charged, while gomesin is a cationic peptide and positively charged. It’s attracted by electrostatic action to the surface of the organism and eventually penetrates the membrane, causing the appearance of pores or the removal of pieces. As a result, the organism loses its link to the outside environment and dies,” Silva said.
Independently of the Brazilian research, Australian scientists are also studying gomesin. In an article published in the journal Cell Death Discovery, they state that both the peptide gomesin (AgGom) found in spiders and a gomesin-like homologue (HiGom) are toxic and antiproliferative for DFTD cells.
The Australian researchers found the peptide in the Australian funnel web spider Hadronyche infensa and synthesized the substance. For the first time, they tested the antiproliferative properties of both AgGom and HiGom as possible candidates for treatment of DFTD.
The proof that gomesin prevents proliferation of DFTD cells is a promise of salvation for the species, which is endangered according to the IUCN Red List.
No treatment is currently available for the disease, which has killed 80% of the Tasmanian devil population since it emerged in 1996. Primary tumors appear on the face or inside the mouth and develop into large globular tumors that rapidly metastasize to internal organs. The disease spreads by transfer of living cancer cells through bites during mating and territorial fighting, leading to death three to six months after the appearance of clinical symptoms.
Modeling studies have estimated that without intervention, the Tasmanian devil will become extinct within 15-25 years unless a treatment for the disease is found.
According to Silva, gomesin was patented at the time of its discovery, and plans to partner with the pharmaceutical industry to commercialize a product have not prospered. “The industry isn’t interested in investing in clinical trials, which are very costly and essential to drug development,” he said.
Source : By Maria Fernanda Ziegler | Agência FAPESP