[{"command":"openDialog","selector":"#drupal-modal","settings":null,"data":"\u003Cdiv id=\u0022republish_modal_form\u0022\u003E\u003Cform class=\u0022modal-form-example-modal-form ecl-form\u0022 data-drupal-selector=\u0022modal-form-example-modal-form\u0022 action=\u0022\/en\/article\/modal\/11804\u0022 method=\u0022post\u0022 id=\u0022modal-form-example-modal-form\u0022 accept-charset=\u0022UTF-8\u0022\u003E\u003Cp\u003EHorizon articles can be republished for free under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence.\u003C\/p\u003E\n \u003Cp\u003EYou must give appropriate credit. We ask you to do this by:\u003Cbr \/\u003E\n 1) Using the original journalist\u0027s byline\u003Cbr \/\u003E\n 2) Linking back to our original story\u003Cbr \/\u003E\n 3) Using the following text in the footer: This article was originally published in \u003Ca href=\u0027#\u0027\u003EHorizon, the EU Research and Innovation magazine\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003ESee our full republication guidelines \u003Ca href=\u0027\/horizon-magazine\/republish-our-stories\u0027\u003Ehere\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003EHTML for this article, including the attribution and page view counter, is below:\u003C\/p\u003E\u003Cdiv class=\u0022js-form-item form-item js-form-type-textarea form-item-body-content js-form-item-body-content ecl-form-group ecl-form-group--text-area form-no-label ecl-u-mv-m\u0022\u003E\n \n\u003Cdiv\u003E\n \u003Ctextarea data-drupal-selector=\u0022edit-body-content\u0022 aria-describedby=\u0022edit-body-content--description\u0022 id=\u0022edit-body-content\u0022 name=\u0022body_content\u0022 rows=\u00225\u0022 cols=\u002260\u0022 class=\u0022form-textarea ecl-text-area\u0022\u003E\u003Ch2\u003ETaking the bite out of snake venom\u003C\/h2\u003E\u003Cp\u003EIn November 2023, police in the southern Dutch city of Tilburg issued an alert about an \u201cextremely venomous\u201d snake that was two metres long and had escaped from its confines.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe green mamba was eventually found behind a plaster wall in the owner\u2019s house, easing public concern and ending what had been a national news item.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMillions of bites\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe incident gave city dwellers in Europe rare exposure to a threat that many millions of people elsewhere face on a regular basis.\u003C\/p\u003E\u003Cp\u003EEvery year around\u0026nbsp;\u003Ca href=\u0022https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/snakebite-envenoming\u0022\u003E5.4 million people globally\u003C\/a\u003E \u2013 often in the world\u2019s poorest communities \u2013 are bitten by venomous snakes, with countries such as Bangladesh, Burkina Faso, India and Nigeria estimated to have large numbers of cases.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EGlobally, these bites cause between 81 000 and 138 000 deaths and around\u0026nbsp;\u003Ca href=\u0022https:\/\/www.lstmed.ac.uk\/the-centre-for-snakebite-research-interventions\u0022\u003E400 000 permanent injuries\u003C\/a\u003E including amputations resulting from severe tissue damage. Snakebite envenoming is deemed a neglected tropical disease by the World Health Organization and is more deadly than all other WHO-recognised neglected tropical diseases.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EProfessor Nicholas Casewell is seeking to reduce these numbers as part of a research project that received EU funding to improve snakebite treatments, which have barely changed in the past 100 years.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u2018If you get the right antivenom quickly enough, then they can be effective \u2013 they are life-saving treatments,\u2019 said Casewell, an expert in snakebites at the Liverpool School of Tropical Medicine in the UK. \u2018But they have so many deficiencies associated with them.\u2019\u003C\/p\u003E\u003Cp\u003EAntivenoms are currently produced by injecting horses or sheep with low doses of venom so that the animals develop antibodies against it. Blood serum containing these antibodies is then collected from the host animals to be used as antivenom \u2013 a process first demonstrated by a French physician named Albert Calmette in the 1890s.\u003C\/p\u003E\u003Cp\u003EAntivenoms are expensive, prove often to be ineffective and need to be kept refrigerated. They can also cause severe adverse reactions such as rashes, joint pain, fever and lymph-node swelling.\u003C\/p\u003E\u003Cp\u003EFurthermore, large pharmaceutical companies have stopped producing antivenoms because they aren\u2019t considered to be financially viable. That increases the need for new treatments.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ENew nanoparticle\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe project in which Casewell is involved brings together research institutes and universities from Belgium, France, Portugal and the UK. Called\u0026nbsp;\u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/id\/899670\u0022\u003EADDovenom\u003C\/a\u003E, it runs for four and a half years until March 2025.\u003C\/p\u003E\u003Cp\u003EThe researchers have turned to a new synthetic nanoparticle to develop more effective snakebite treatments. Virus-like, it is known as an ADDomer.\u003C\/p\u003E\u003Cp\u003EADDomers are self-assembling because they are made up of many copies of the same protein. These proteins can be modified in a way that enables them to grab and neutralise specific targets.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EIn the case of ADDovenom, those targets are the toxins in snake venom.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EVipers and mambas\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe project focuses on the saw-scaled vipers and mambas of Africa. They cause a substantial medical burden among snakes in the sub-Saharan region.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EWe can extract the most abundant and most pathogenic toxins.\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProfessor Christiane Berger-Schaffitzel, ADDovenom \u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\u003Cp\u003ESaw-scaled vipers signal when they feel threatened and may bite by coiling into a pretzel shape and rubbing their scales together \u2013 an action that creates a sizzling sound.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EMambas, which are closely related to cobras, seek to scare off aggressors by rearing up and hissing.\u003C\/p\u003E\u003Cp\u003EThe venom from these two types of snakes has very different effects. In saw-scaled vipers it causes internal bleeding, while in mambas it triggers paralysis.\u003C\/p\u003E\u003Cp\u003EUnder ADDovenom, proteomics experts at the University of Liege in Belgium have been analysing the venom of these snakes harvested at the herpetarium at the Liverpool School of Tropical Medicine, which houses the largest collection of venomous snakes in the UK and is one of the most diverse in Europe.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EVenoms are a mix of different components. The project\u2019s goal is to identify and neutralise the most dangerous toxins in saw-scaled vipers and mambas.\u003C\/p\u003E\u003Cp\u003E\u2018We now know the composition of these venoms and we can extract the most abundant and most pathogenic toxins,\u2019 said Professor Christiane Berger-Schaffitzel, a biochemist at the UK-based University of Bristol who runs the project. \u2018These are our targets.\u2019\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMore effective, affordable\u0026nbsp;\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003ECurrent antivenoms work in anything but a targeted fashion.\u003C\/p\u003E\u003Cp\u003EAt most only around a third of antivenom antibodies target snake venom. The rest are antibodies that the animals from which the antivenom was created had circulating in their bodies to fight off other pathogens.\u003C\/p\u003E\u003Cp\u003EThis, combined with the fact that the antibodies are animal-derived, is why antivenoms can make people sick. Patients develop a condition known as serum sickness, which is an allergic reaction to these additional and unnecessary components in the animal serum.\u0026nbsp;\u003C\/p\u003E\u003Cfigure role=\u0022group\u0022\u003E\n\u003Cimg alt=\u0022Extracting venom from a saw-scaled viper. \u00a9 Simon Townsley\u0022 data-entity-type=\u0022file\u0022 data-entity-uuid=\u00223f5e5a0b-41da-4c33-9744-19b62a9d6af0\u0022 height=\u00221320\u0022 src=\u0022\/sites\/default\/files\/hm\/IMCEUpload\/Echis%20coloratus_S.%20Townsley_3_Extraction.JPG\u0022 width=\u00221980\u0022\u003E\n\u003Cfigcaption class=\u0022tw-italic tw-mb-4\u0022\u003EExtracting venom from a saw-scaled viper. \u00a9 Simon Townsley\u003C\/figcaption\u003E\n\u003C\/figure\u003E\n\u003Cp\u003E\u2018Here we are trying to do things in a much more rational, informed way,\u2019 Casewell said.\u003C\/p\u003E\u003Cp\u003EThe researchers hope that, as well as being more effective, their planned treatments will be safer.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EAnd because ADDomers remain stable at high temperatures, the treatments wouldn\u2019t need to be refrigerated, making them more accessible to remote rural communities in the tropics.\u003C\/p\u003E\u003Cp\u003EWhile the project will wrap up in less than a year, the research won\u2019t.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EAs well as further developing ADDomer nanoparticles for different toxins, the scientists will examine how these products could be manufactured to scale to keep them affordable.\u003C\/p\u003E\u003Cp\u003E\u2018The cost is really important because we are talking about developing countries and rural areas,\u2019 Berger-Schaffitzel said. \u2018People definitely have problems affording treatment.\u2019\u003C\/p\u003E\u003Cp\u003EJust when ADDomer-based treatments will become available depends on matters such as the protection they confer in mice against the toxins and the viper venom. For a life-saving treatment, the goal is a broad reactivity across venoms from different vipers. \u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ELab-made antibodies\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EADDomers aren\u2019t the only hope for developing new ways to tackle snakebites.\u003C\/p\u003E\u003Cp\u003EOther EU-funded researchers are trying to do so with human monoclonal antibodies. These are laboratory-produced clones of the human body\u2019s countless antibodies.\u003C\/p\u003E\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EThe next big research question is how to manufacture these things cheaply.\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProfessor Andreas Hougaard Laustsen-Kiel, MABSTER\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\u003Cp\u003E\u2018We have antibodies in our blood, but it is a mix of millions of different antibodies,\u2019 said Andreas Hougaard Laustsen-Kiel, a professor in antibody technologies at the Technical University of Denmark. \u2018A monoclonal one is just one of these many, many antibodies.\u2019\u003C\/p\u003E\u003Cp\u003EEngineered monoclonal antibodies are already used in several areas of medicine, mainly as targeted therapies for cancer and as treatments for autoimmune diseases including rheumatoid arthritis.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ELaustsen-Kiel and colleagues are engineering antibodies that neutralise multiple related toxins in snake venoms.\u003C\/p\u003E\u003Cp\u003E\u2018It is relatively straightforward to find a monoclonal antibody that just binds one target,\u2019 he said. \u2018The more difficult thing is to find a monoclonal antibody that binds several different targets.\u2019\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ETheir project,\u0026nbsp;\u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/id\/850974\u0022\u003EMABSTER\u003C\/a\u003E, is due to wrap up in December 2024 after five years.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EAs with ADDovenom, the researchers have been focusing on snake toxins that cause a significant medical burden.\u003C\/p\u003E\u003Cp\u003EMABSTER has developed and tested on mice a mixture of antibodies that can neutralise coral snake venoms, a family of brightly coloured, highly venomous snakes that live in the Americas.\u003C\/p\u003E\u003Cp\u003EThe team is also close to completing a mix for treating bites from African cobras and mambas, according to Laustsen-Kiel.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EFewer side effects\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EIn addition to engineering the antibodies to target specific toxins, the team is trying to ensure the antibodies survive longer in the body to fight new toxins again.\u003C\/p\u003E\u003Cp\u003ENormally, after an antibody has bound to its target, known as an antigen \u2013 in this case a venom toxin \u2013 it neutralises the antigen and signals it for destruction. In this process, the antibody remains occupied by the antigen until both are destroyed.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EBy engineering the monoclonal antibodies to be sensitive to their microenvironment, it\u2019s possible to programme them so that they release the antigen during cellular recycling of the antibody-antigen complex, according to Laustsen-Kiel.\u003C\/p\u003E\u003Cp\u003EThis leaves the antibody intact and free to go and bind more toxins.\u003C\/p\u003E\u003Cp\u003ERecycling antibodies in this way could allow lower doses of treatment to be used, increasing efficacy and potentially reducing side effects.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ELaustsen-Kiel echoed Berger-Schaffitzel by stressing the importance of affordability when it comes to such treatments.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u2018The next big research question is how to manufacture these things cheaply,\u2019 he said.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EResearch in this article was funded by the EU\u2019s Horizon Programme including, in the case of MABSTER, via the European Research Council (ERC). The views of the interviewees don\u2019t necessarily reflect those of the European Commission. 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