Deadly Venom is Being Turned into Life-Saving Medical Treatments
Researchers continue to explore ways to turn deadly venom into life-saving drugs. Several papers on the subject have recently been published and BioSpace takes a look at them below.
Venom is typically made up of very complex chemicals, and it’s fairly common for them to be evaluated for use as drugs. One of the classic cases of this is an entire class of drugs, GLP-1 agonists used to treat diabetes.
Examples of GLP-1 agonists include AstraZeneca’s Byetta (exenatide), Novo Nordisk’s Victoza (liraglutide) and Ozempic (semaglutide), Sanofi’s Lyxumia (lixisenatide), and Eli Lilly’s Trulicity (dulaglutide). The class was originally discovered by Dr. John Eng, M.D. while working in Rosalyn Yalow, Ph.D.’s laboratory at the Mount Sinai School of Medicine. Eng’s research in the 1980s focused on peptide hormones, whereas he was advancing 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 Gila monster venom. One he named exendin-4. It was like GLP-1 and eventually was licensed to Amylin Pharmaceuticals and was developed into Exenatide, the first GLP-1 analog, approved in the U.S. in 2005.
In 2020, researchers at 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 therapeutics directed T cells to target brain tumor cells. Typically, CAR T uses a monoclonal antibody sequence to target the desirable cancer antigens. Their compound leverages a 36-amino acid peptide sequence that was isolated from deathstalker scorpion venom, then engineered to act as the CAR recognition domain. The researchers presented plans at the 2021 ASCO Annual Meeting to launch a Phase I study of the therapy in patients with MMP2+ recurrent or progressive glioblastoma. According to ClinicalTrials.gov, it is still actively recruiting patients.
More recently, other cases of animal venom being evaluated for medical value have been published.
Researchers with Wenzhou Medical University in China published research on the use of telocinobufagin, or Bufo toad venom (Bufo gargarizans), in non-small cell lung cancer (NSCLC). The compound is the active ingredient in the Chinese traditional 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 STAT3 phosphorylation as tyrosine 705 and its downstream targets. They concluded, “These results support telocinobufagin as a promising STAT3 signaling inhibitor candidate for the treatment of NSCLC patients.”
Investigators with The Hebrew University of Jerusalem published research on the use of chemicals isolated from Russell’s viper (Vipera daboia) venom to help mediate some of the side effects associated with multiple sclerosis (MS) drugs. “Treatment with the monoclonal antibodies natalizumab (Tysabri) for therapy of MS and vedolizumab (Entyvio) for IBD, which inhibit alpha4beta1 and alpha4beta7, respectively, has been found to be efficient in the clinic for therapy of chronic relapsing inflammation of demyelinating MS disorders and treatment of resistant Crohn’s disease. However, the therapeutic efficacy of natalizumab is associated with adverse effects,” the article said.
They isolated a chemical called visabron c from the viper venom, then tested it in an experimental autoimmune encephalomyelitis (EAE) animal model. Their research suggests the compound might be a safe alternative peptidomimetic to monoclonal anti-alpha4 integrin antibodies, steroids, and other immunosuppressant drugs. They also think it might “pave the way for developing 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 investigated a treatment for multidrug-resistant bacteria based on a synthetic peptide derived from scorpion (Opisthacanthus madagascariensis) venom. Its toxicity was generally too high for use, but they engineered a peptide derived from it and demonstrated that it had significantly lower toxicity toward humans while having increased antimicrobial activity against Gram-negative and Gram-positive bacteria in victor and improved anti-infective activity in a mouse model. They found that the antimicrobial activity was due, in part, to an improved 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 for eliciting analgesia in patients suffering from chronic visceral pain,” the researchers wrote.