Defining the pathophysiology of venom-induced chronic wounds to inform new treatments for snakebite victims

Snakebite, designated as a neglected tropical disease by the World Health Organization (WHO), claims approximately 137,000 lives annually and leaves up to 500,000 victims with permanent disabilities and disfigurements due to local tissue damage. The impact is most severe in rural, low/middle-income tropical regions, where snakebite-related morbidity has devastating socioeconomic consequences through loss of income, interrupted education, and social stigma. In response, the WHO has set a goal to halve snakebite deaths and disabilities. Local envenoming occurs when venom toxins either directly damage cells, disrupt blood vessels or trigger inflammatory responses. This can cause extensive swelling, blistering and tissue death around the bite site. Whilst normal wound healing is an uneventful process typically resulting in scar formation, an estimated 3–6% of snakebite victims develop chronic wounds. Treatment options for these patients are limited to invasive surgery or even amputation, as antivenom therapy is considered ineffective unless rapidly administered after the bite. Despite the severity of this issue, the underlying cellular and molecular mechanisms of snakebite wound formation and healing remain poorly understood. Our project will address this knowledge gap through comprehensive characterization of preclinical and clinical snakebite wounds. We have recently established novel preclinical models of venom-induced chronic wounds using three medically important venoms (Dawson et al, 2025). We will expand this research by analysing clinical wound biopsies from snakebite patients in Brazilian Amazon hospitals. These samples will enable us to spatially visualise and quantify the microscopic change in tissues, identify genes associated with chronic wound development, and understand how local envenoming affects healing processes and inflammation. We will also compare our findings with data from chronic wounds caused by other conditions to identify any common and distinct pathological patterns. Using our preclinical venom chronic wound models, we will evaluate both existing and novel therapeutic approaches. While antivenom is currently the only approved treatment, its effectiveness in preventing tissue damage is limited by speed of administration post-bite. Our research will, for the first time, determine the precise time window that antivenom treatment delivers therapeutic benefit after a snakebite, helping to guide local envenoming management in the clinic. Additionally, we will investigate the efficacy and mechanism of action of novel therapeutics that support the healing pathway, with our preliminary results showing that MC1R agonist delivery positively impacts closure of chronic venom wounds. This research directly supports the WHO’s goal of reducing snakebite deaths and disabilities. Our project will contribute significantly by systematically analyzing snakebite chronic wound pathophysiology in both novel preclinical models and human biopsies. Our evaluation of antivenom efficacy will inform treatment policy for local envenoming, while our investigation of novel therapeutics could improve outcomes for snakebite patients across the remote, rural tropics.