Interview: Snakebite as a Priority NTD

September 18, 2020

Doctor Rachel Clare and Professor Nicholas Casewell, two scholars working at the forefront of international snakebite research, speak on the challenges, opportunities and new avenues in the field.

Extraction of the venom (Photo: Kristin Kidd)

Recognised as one of the priority neglected tropical diseases (NTDs) by the World Health Organization (WHO) in 2017, snakebite affects 4.5–5.4 million people globally each year. Snakebites cause approximately 100,000 deaths annually, and leave as many as half a million survivors left with long-term disabilities, linked to amputations, kidney damage, and other sequelae.

WIPO Re:Search asked Dr. Clare and Professor Casewell about their groundbreaking work underway in the WIPO Re:Search-facilitated partnership between the Liverpool School of Tropical Medicine (LSTM) and Johnson & Johnson to advance international research for effective treatments against snakebite envenoming. Snakebite envenoming is a life-threatening condition that results from the injection of venom (a mixture of different toxins) following the bite of a venomous snake.

Short bio of Dr. Rachel Clare

(Photo: Aiden Ogden)

Doctor Rachel Clare is a postdoctoral researcher at the Centre for Snakebite Research & Interventions (CSRI) at LSTM. Her current research -- which recently won financial support from the LSTM Directors Catalyst Fund -- focuses on the discovery of novel small-molecule based treatments for snakebite. Dr. Clare earned a PhD from the University of Sheffield for her work on drug discovery for tropical parasitic diseases, namely onchocerciasis and lymphatic filariasis.

Short bio of Prof. Nicholas Casewell

(Photo: Liverpool School of Tropical Medicine)

Professor Nicholas Casewell is the Director of CSRI at LSTM. He holds a PhD from Bangor University, UK, for his work on snake venom and snakebite treatments. Prof. Casewell has several years of experience as an antivenom product lead at MicroPharm Limited, a UK-based antivenom manufacturer. He has worked since 2014 at LSTM on the development of more efficacious therapeutics for treating snakebites.

Could you provide a brief description of your ongoing WIPO Re:Search facilitated research?

Rachel: Over recent years, the snakebite field has produced promising evidence that drugs originally developed for other indications, such as cancer, heart disease and heavy metal poisoning, could be repurposed for R&D on novel treatments for snakebite. Many of these drugs have potential advantages over current traditional antivenoms (venom-specific antibody therapies). Such advantages include lower cost and safer, easier-to-administer treatments for potential use outside of hospital settings, thus dramatically shortening the critical time from bite to treatment. To date, snakebite drug discovery has focused on testing only a handful of repurposed drugs that are either currently available on the market, or being tested in clinical trials. There exists huge potential for further testing.

To this end, WIPO Re:Search facilitated our collaboration with the pharmaceutical company Johnson & Johnson, which provided access to IP assets in two of their drug libraries to test for inhibitory activity against snake venom. The first library contains a collection of ~1,000 drugs that have extensive testing data from prior drug discovery programs; the second is a collection of ~500 drugs that are predicted to target one of the key toxins (snake venom metalloproteinases) found in venom from a wide range of snake species. New drug leads that may result from this collaboration could offer great potential to limit the devastating impact of snakebite globally.

Nick: Existing snakebite treatments consist of polyclonal antibodies, which, while often effective, are associated with many limitations, such as the requirement for intravenous delivery in a healthcare setting. Our recent research has explored the potential of utilising small molecule toxin inhibitors (existing drugs) as new treatments for snakebite. Through using a drug repurposing approach, our pilot studies have demonstrated that such drugs can protect experimentally envenomed animals from lethal venom effects. The WIPO Re:Search-facilitated collaboration with Johnson & Johnson has enabled us to begin exploring the wider chemical space (collection of drugs) for the identification of new snakebite therapeutics. We hope this research will result in the delivery of orally delivered, community-based therapies to tackle this life-threatening medical emergency.

What opportunities do you see in snakebite-related research in the coming years?

Rachel: Having worked on drug discovery for other NTDs, such as lymphatic filariasis and onchocerciasis, I believe that there are many tried and tested strategies that snakebite drug discovery can use as this field builds and broadens. These include academic-industrial partnerships, such as our collaboration with Johnson & Johnson. Similar to the current collaboration, the supply, at no cost, of drug collections by pharmaceutical companies to academics for testing will support the identification of the best possible drugs to address snakebite.

Nick: The biggest change has come in the past three years following the WHO announcement that recognized snakebite as a priority NTD. This declaration engendered considerable publicity and advocacy relating to snakebite, which has lacked attention for many decades, despite being the most lethal of all of the NTDs. In turn, this has generated public interest from global funders. The snakebite community is now in a position where there is considerable potential to deliver long-lasting, impactful interventions that will benefit the lives and livelihoods of impoverished tropical populations that suffer the greatest burden of snakebite.

I believe that snakebite has an opportunity to be the next NTD success story; it will require a long-term approach – snakebite cannot be eradicated. Collectively, as a global community, over the coming years, we have an opportunity to devise and deliver impactful interventions to mitigate the detrimental impact of snakebite on some of the world’s most vulnerable populations. We must not miss this opportunity.

(Photo: Ben Gilbert)

What are some unique challenges of snakebite envenoming research?

Rachel: Cost constitutes the biggest challenge for progressing from initial high-throughput screening to human clinical trials. Without substantial funding and support (e.g. sharing of drug libraries) from pharmaceutical companies, exciting opportunities could be missed.

Nick: I believe that one of the major challenges with snakebite is the complexity of venom. Multiple toxins are present simultaneously in any one venom, and vary considerably among snake species (there are around 100-200 species capable of causing life threatening bites). In fact, there are examples where the venom of the same species is markedly different between two populations separated by less than 100 miles. 

This causes major difficulties for snakebite therapeutics, given the huge diversity of toxins in any given geographical area that require neutralization. Moreover, the lack of snakebite diagnostics renders unfeasible tailor-made therapeutic solutions. Current antivenom treatments are geographically restricted in terms of their efficacy. One of the main goals of our research is to apply our basic biological knowledge of venom composition to devise global solutions for treating snakebite.

What are your expectations and hopes for young researchers in your field?

Rachel: From a drug discovery perspective, it is a really exciting time to join the snakebite field, with the future holding the very real prospect of a snakebite drug that is affordable and accessible for those most neglected in our global society.

Nick: In snakebite, young researchers have the opportunity to perform impactful research that will influence policy over the coming years – a historical lack of investment in the field means that there are major gains to be made in a relatively short period of time. This NTD is recognized as a global health challenge that warrants investment and attention to effect change for victims. In terms of therapeutics, it is also extremely exciting because various strategies show considerable promise as ‘next-generation’ replacements for current antivenom.

What helps you keep moving forward with your research every day?

Rachel: I am motivated by the potential to contribute to the portfolio of drugs to address the preventable severity of this priority NTD, which devastates the lives of victims and their families due to the loss of loved ones, disability and/or financial debt following the cost of treatment or loss of earnings. On a day-to-day basis, I am also incredibly motivated by the environment at CSRI, where I work in a vibrant laboratory alongside other innovative and supportive early career toxinologists.

Nick: There are several motivations for our work. One of the biggest is understanding the scale of snakebite’s impact – millions of people are affected by it every single year. Visiting snakebite-affected regions leaves a lasting motivation. Everyone in these areas knows of someone who has been affected by snakebite. Talking to families of deceased victims or disfigured survivors is a sobering and often distressing experience that leaves us with lasting memories. The science itself is also a motivator that keeps us moving forward. Mitigating snakebite is extremely challenging due to the various aforementioned factors, but that in and of itself is exciting and stimulating. Finally, I have the pleasure of working with a diverse team of passionate and driven individuals who move our research forward daily.

About WIPO Re:Search

WIPO Re:Seach is a global public-private partnership between WIPO and BIO Ventures for Global Health (BVGH), a non-profit organization that connects the for-profit and non-profit sectors to solve global health challenges. WIPO Re:Search supports early-stage research and development (R&D) in the fight against neglected tropical diseases (NTDs), malaria, and tuberculosis. Through targeted, mutually beneficial R&D collaborations among its members, the partnership catalyses royalty-free sharing of IP – including compounds, data, clinical samples, technology, and expertise – and drives progress towards the UN Sustainable Development goals.

This collaboration between researchers at Johnson & Johnson and those at LSTM’s Centre for Snakebite Research & Interventions is WIPO Re:Search’s first snakebite collaboration.