• Tue. Sep 27th, 2022

Deadly venom is turned into life-saving medical treatments

ByMadeleine J. Pierce

May 17, 2022

Researchers continue to explore ways to turn deadly venom into life-saving drugs. Several articles on the subject have recently appeared, and BioSpace reviews them below.

Venom is usually made up of very complex chemicals and it is quite common for them to be tested for use as medicine. One of the classic cases is that of a all the class drugs, GLP-1 agonists used to treat diabetes.

Examples of GLP-1 agonists include Astra Zeneca‘s Byetta (exenatide), Novo Nordisk‘s Victoza (liraglutide) and Ozempic (semaglutide), SanofiLyxumia (lixisenatide), and Eli Lily‘s Trulicity (dulaglutide). The class was originally discovered by Dr. John Eng, MD while working in the laboratory of Rosalyn Yalow, Ph.D. at Mount Sinai School of Medicine. Eng’s research in the 1980s focused on peptide hormones, as he advanced Yalow’s research by developing more sensitive tests to help identify hormones. Initially he worked with guinea pigs and chinchillas, then moved on to snake and lizard venom, particularly Gila monster venom.

In 1982, Eng identified two compounds in the venom of the Gila monster. One he named exendin-4. It was like GLP-1 and was eventually cleared to Amyline Pharmaceuticals and was developed into Exenatide, the first GLP-1 analogue, approved in the United States in 2005.

In 2020, researchers from city ​​of hope developed a chimeric antigen receptor (CAR) T-cell therapy using chlorotoxin (CLTX), a component of scorpion venom. In research published in Science Translational Medicine, they described how the therapeutic directed T cells to targeted brain tumor cells. Typically, CAR T uses a monoclonal antibody sequence to target desirable cancer antigens. Their compound exploits a 36 amino acid peptide sequence that was isolated from the deadly stalker’s scorpion venom and then engineered to act as a CAR recognition domain. Researchers plans presented at the 2021 ASCO Annual Meeting to initiate a Phase I study of the therapy in patients with recurrent or progressive MMP2+ glioblastoma. According ClinicalTrials.govhe is still actively recruiting patients.

More recently, other cases of animal venom being evaluated for their medical value have been published.

Researchers from Wenzhou Medical University in China published research on the use of telocinobufagine, or Bufo toad venom (Bufo gargarizans), in non-small cell lung cancer (NSCLC). The compound is the active ingredient in traditional Chinese medicine ChanSu and has antitumor effects, but the mechanism of action is unknown. They found that telocinobufagin suppressed proliferation and metastasis, and also induced cell death (apoptosis) in human NSCLC cells. It also significantly inhibited the phosphorylation of STAT3 as tyrosine 705 and its downstream targets. They concluded, “These results support telocinobufagine as a promising STAT3 signaling inhibitor candidate for the treatment of patients with NSCLC.”

Investigators with The Hebrew University of Jerusalem published research into the use of chemicals isolated from Russell’s viper (Vipera daboia) venom to help alleviate some of the side effects associated with multiple sclerosis (MS) medications. “Treatment with the monoclonal antibodies natalizumab (Tysabri) for the treatment of MS and vedolizumab (Entyvio) for IBD, which inhibit alpha4beta1 and alpha4beta7, respectively, have been shown to be clinically effective for the treatment of chronic recurrent inflammation demyelinating disorders in MS and treatment of resistant Crohn’s disease. However, the therapeutic efficacy of natalizumab is associated with adverse effects,” the article states.

They isolated a chemical called visabron c from viper venom and then tested it in an experimental animal model of autoimmune encephalomyelitis (EAE). Their research suggests that the compound could be a safe alternative peptidomimetic to anti-alpha4 integrin monoclonal antibodies, steroids and other immunosuppressive drugs. They also believe it could “pave the way for the development of new therapies for a variety of other inflammatory and/or autoimmune diseases.”

Scientists from the University of Pennsylvania and Universidade Federal do ABC in Brazil investigation a treatment for multiresistant bacteria based on a synthetic peptide derived from scorpion venom (Opisthacanthus madagascariensis). Its toxicity was generally too high to use, but they designed a peptide derived from it and demonstrated that it had significantly lower toxicity towards humans while having increased antimicrobial activity against Gram-negative bacteria and Gram-positives in victor and improved anti-infective activity in a mouse model. They found that the antimicrobial activity was due, in part, to an enhanced ability to “permeabilize the outer membrane and depolarize the cytoplasmic membrane.”

And finally, researchers from the University of Queensland and the University of Adelaide in Australia studied the use of Peruvian tarantula (Avicularia juruensis) venom to treat pain associated with irritable bowel syndrome. They isolated a novel hNav1.7 inhibitor, Tsp1a, from tarantula venom. Intracolonic administration of the compound in a mouse model of irritable bowel syndrome completely reversed chronic visceral hypersensitivity. “The ability of Tsp1a to reduce visceral hypersensitivity in a model of irritable bowel syndrome suggests that pharmacological inhibition of hNav1.7 at peripheral sensory nerve endings might be a viable approach to induce analgesia in patients with irritable bowel syndrome. chronic visceral pain,” the researchers wrote.