{"id":12457,"date":"2024-08-21T10:00:00","date_gmt":"2024-08-21T10:00:00","guid":{"rendered":"https:\/\/modernsciences.org\/staging\/4414\/?p=12457"},"modified":"2024-08-11T14:44:00","modified_gmt":"2024-08-11T14:44:00","slug":"a-common-parasite-could-one-day-deliver-drugs-to-the-brain-how-scientists-are-turning-toxoplasma-gondii-from-foe-into-friend","status":"publish","type":"post","link":"https:\/\/modernsciences.org\/staging\/4414\/a-common-parasite-could-one-day-deliver-drugs-to-the-brain-how-scientists-are-turning-toxoplasma-gondii-from-foe-into-friend\/","title":{"rendered":"A common parasite could one day deliver drugs to the brain \u2212 how scientists are turning Toxoplasma gondii from foe into friend"},"content":{"rendered":"\n<div class=\"theconversation-article-body\">\n    <figure>\n      <img  decoding=\"async\"  src=\"data:image\/png;base64,iVBORw0KGgoAAAANSUhEUgAAAAEAAAABAQMAAAAl21bKAAAAA1BMVEUAAP+KeNJXAAAAAXRSTlMAQObYZgAAAAlwSFlzAAAOxAAADsQBlSsOGwAAAApJREFUCNdjYAAAAAIAAeIhvDMAAAAASUVORK5CYII=\"  class=\" pk-lazyload\"  data-pk-sizes=\"auto\"  data-pk-src=\"https:\/\/images.theconversation.com\/files\/610930\/original\/file-20240801-23-p71s74.jpg?ixlib=rb-4.1.0&#038;rect=0%2C0%2C2121%2C1412&#038;q=45&#038;auto=format&#038;w=754&#038;fit=clip\" >\n        <figcaption>\n          <em>Toxoplasma<\/em> is often transmitted to people from contaminated food or cat feces.\n          <span class=\"attribution\"><a class=\"source\" href=\"https:\/\/www.gettyimages.com\/detail\/photo\/parasitic-protozoans-toxoplasma-gondii-royalty-free-image\/1392928028\" target=\"_blank\" rel=\"noopener\">Dr_Microbe\/iStock via Getty Images Plus<\/a><\/span>\n        <\/figcaption>\n    <\/figure>\n\n  <span><a href=\"https:\/\/theconversation.com\/profiles\/bill-sullivan-703249\" target=\"_blank\" rel=\"noopener\">Bill Sullivan<\/a>, <em><a href=\"https:\/\/theconversation.com\/institutions\/indiana-university-1368\" target=\"_blank\" rel=\"noopener\">Indiana University<\/a><\/em><\/span>\n\n  <p>Parasites <a href=\"https:\/\/doi.org\/10.1371\/journal.pmed.1001920\" target=\"_blank\" rel=\"noopener\">take an enormous toll<\/a> on human and veterinary health. But researchers may have found a way for patients with brain disorders and a common brain parasite to become frenemies.<\/p>\n\n<p>A new study published in <a href=\"https:\/\/doi.org\/10.1038\/s41564-024-01750-6\" target=\"_blank\" rel=\"noopener\">Nature Microbiology<\/a> has pioneered the use of a single-celled parasite, <em>Toxoplasma gondii<\/em>, to inject therapeutic proteins into brain cells. The <a href=\"https:\/\/theconversation.com\/our-blood-brain-barrier-stops-bugs-and-toxins-getting-to-our-brain-heres-how-it-works-230965\" target=\"_blank\" rel=\"noopener\">brain is very picky<\/a> about what it lets in, including many drugs, which limits treatment options for neurological conditions.<\/p>\n\n<p>As a <a href=\"https:\/\/medicine.iu.edu\/faculty\/13502\/sullivan-william\" target=\"_blank\" rel=\"noopener\">professor of microbiology<\/a>, I\u2019ve dedicated my career to finding ways to kill dangerous parasites such as <em>Toxoplasma<\/em>. I\u2019m fascinated by the prospect that we may be able to use their weaponry to instead treat other maladies.<\/p>\n\n<h2 id=\"microbes-as-medicine\">Microbes as medicine<\/h2>\n\n<p>Ever since scientists realized that microscopic organisms can cause illness \u2013 what\u2019s called the 19th-century <a href=\"https:\/\/curiosity.lib.harvard.edu\/contagion\/feature\/germ-theory\" target=\"_blank\" rel=\"noopener\">germ theory of disease<\/a> \u2013 humanity has been on a quest to keep infectious agents out of our bodies. Many people\u2019s understandable aversion to germs may make the idea of adapting these microbial adversaries for therapeutic purposes seem counterintuitive.<\/p>\n\n<p>But preventing and treating disease by co-opting the very microbes that threaten us has a history that long predates germ theory. <a href=\"https:\/\/doi.org\/10.1258%2Fjrsm.2012.12k044\" target=\"_blank\" rel=\"noopener\">As early as the 1500s<\/a>, people in the Middle East and Asia noted that those lucky enough to survive smallpox never got infected again. These observations led to the practice of purposefully exposing an uninfected person to the material from an infected person\u2019s pus-filled sores \u2013 which unbeknownst to them contained weakened smallpox virus \u2013 to protect them from severe disease. <\/p>\n\n<figure class=\"align-center zoomable\">\n            <a href=\"https:\/\/images.theconversation.com\/files\/610942\/original\/file-20240801-17-u4nsur.jpg?ixlib=rb-4.1.0&amp;q=45&amp;auto=format&amp;w=1000&amp;fit=clip\" target=\"_blank\" rel=\"noopener\"><img  decoding=\"async\"  alt=\"Scan of yellowed book pages with illustration of person covered in smallpox pustules on left page and Japanese text on the right\"  src=\"data:image\/png;base64,iVBORw0KGgoAAAANSUhEUgAAAAEAAAABAQMAAAAl21bKAAAAA1BMVEUAAP+KeNJXAAAAAXRSTlMAQObYZgAAAAlwSFlzAAAOxAAADsQBlSsOGwAAAApJREFUCNdjYAAAAAIAAeIhvDMAAAAASUVORK5CYII=\"  class=\" pk-lazyload\"  data-pk-sizes=\"auto\"  data-ls-sizes=\"(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px\"  data-pk-src=\"https:\/\/images.theconversation.com\/files\/610942\/original\/file-20240801-17-u4nsur.jpg?ixlib=rb-4.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;fit=clip\"  data-pk-srcset=\"https:\/\/images.theconversation.com\/files\/610942\/original\/file-20240801-17-u4nsur.jpg?ixlib=rb-4.1.0&amp;q=45&amp;auto=format&amp;w=600&amp;h=450&amp;fit=crop&amp;dpr=1 600w, https:\/\/images.theconversation.com\/files\/610942\/original\/file-20240801-17-u4nsur.jpg?ixlib=rb-4.1.0&amp;q=30&amp;auto=format&amp;w=600&amp;h=450&amp;fit=crop&amp;dpr=2 1200w, https:\/\/images.theconversation.com\/files\/610942\/original\/file-20240801-17-u4nsur.jpg?ixlib=rb-4.1.0&amp;q=15&amp;auto=format&amp;w=600&amp;h=450&amp;fit=crop&amp;dpr=3 1800w, https:\/\/images.theconversation.com\/files\/610942\/original\/file-20240801-17-u4nsur.jpg?ixlib=rb-4.1.0&amp;q=45&amp;auto=format&amp;w=754&amp;h=566&amp;fit=crop&amp;dpr=1 754w, https:\/\/images.theconversation.com\/files\/610942\/original\/file-20240801-17-u4nsur.jpg?ixlib=rb-4.1.0&amp;q=30&amp;auto=format&amp;w=754&amp;h=566&amp;fit=crop&amp;dpr=2 1508w, https:\/\/images.theconversation.com\/files\/610942\/original\/file-20240801-17-u4nsur.jpg?ixlib=rb-4.1.0&amp;q=15&amp;auto=format&amp;w=754&amp;h=566&amp;fit=crop&amp;dpr=3 2262w\" ><\/a>\n            <figcaption>\n              <span class=\"caption\">The concept of inoculation developed with smallpox outbreaks several centuries ago.<\/span>\n              <span class=\"attribution\"><a class=\"source\" href=\"https:\/\/wellcomecollection.org\/works\/cq7sx6ak\/images?id=crcz8r3s\" target=\"_blank\" rel=\"noopener\">MS Japanese 63\/Wellcome Collection<\/a>, <a class=\"license\" href=\"http:\/\/creativecommons.org\/licenses\/by\/4.0\/\" target=\"_blank\" rel=\"noopener\">CC BY<\/a><\/span>\n            <\/figcaption>\n          <\/figure>\n\n<p>This <a href=\"https:\/\/theconversation.com\/benjamin-franklins-fight-against-a-deadly-virus-colonial-america-was-divided-over-smallpox-inoculation-but-he-championed-science-to-skeptics-161569\" target=\"_blank\" rel=\"noopener\">concept of inoculation<\/a> <a href=\"https:\/\/theconversation.com\/lady-mary-wortley-montagu-the-forgotten-immunisation-pioneer-164256\" target=\"_blank\" rel=\"noopener\">has yielded a<\/a> <a href=\"https:\/\/www.cdc.gov\/vaccines\/vpd\/vaccines-list.html\" target=\"_blank\" rel=\"noopener\">plethora of vaccines<\/a> that have saved countless lives.<\/p>\n\n<p>Viruses, bacteria and parasites have also evolved many tricks to penetrate organs such as the brain and could be <a href=\"https:\/\/doi.org\/10.1007%2Fs40199-019-00291-2\" target=\"_blank\" rel=\"noopener\">retooled to deliver drugs<\/a> into the body. Such uses could include <a href=\"https:\/\/doi.org\/10.1038\/s41392-021-00487-6\" target=\"_blank\" rel=\"noopener\">viruses for gene therapy<\/a> and <a href=\"https:\/\/doi.org\/10.1016\/S2468-1253(22)00276-X\" target=\"_blank\" rel=\"noopener\">intestinal bacteria to treat a gut infection<\/a> known as <a href=\"https:\/\/www.cdc.gov\/c-diff\/index.html\" target=\"_blank\" rel=\"noopener\"><em>C. diff<\/em><\/a>.  <\/p>\n\n<h2 id=\"why-cant-we-just-take-a-pill-for-brain-diseases\">Why can\u2019t we just take a pill for brain diseases?<\/h2>\n\n<p>Pills offer a convenient and effective way to get medicine into the body. <a href=\"https:\/\/www.drugs.com\/drug-classes.html#B\" target=\"_blank\" rel=\"noopener\">Chemical drugs<\/a> such as aspirin or penicillin are small and easily absorbed from the gut into the bloodstream.<\/p>\n\n<p><a href=\"https:\/\/theconversation.com\/biologics-the-pricey-drugs-transforming-medicine-80258\" target=\"_blank\" rel=\"noopener\">Biologic drugs<\/a> such as insulin or semaglutide, on the other hand, are large and complex molecules that are vulnerable to breaking down in the stomach before they can be absorbed. They are also too big to pass through the intestinal wall into the bloodstream.<\/p>\n\n<p>All drugs, especially biologics, have great difficulty penetrating the brain due to the <a href=\"https:\/\/theconversation.com\/our-blood-brain-barrier-stops-bugs-and-toxins-getting-to-our-brain-heres-how-it-works-230965\" target=\"_blank\" rel=\"noopener\">blood-brain barrier<\/a>. The blood-brain barrier is a layer of cells lining the brain\u2019s blood vessels that acts like a gatekeeper to block germs and other unwanted substances from gaining access to neurons.<\/p>\n\n<h2 id=\"toxoplasma-offers-delivery-service-to-brain-cells\"><em>Toxoplasma<\/em> offers delivery service to brain cells<\/h2>\n\n<p><em>Toxoplasma<\/em> parasites <a href=\"https:\/\/doi.org\/10.1079\/ahr2005100\" target=\"_blank\" rel=\"noopener\">infect all animals, including humans<\/a>. Infection can occur in multiple ways, including ingesting spores released in the stool of infected cats or consuming contaminated meat or water. <a href=\"https:\/\/www.cdc.gov\/toxoplasmosis\/about\/index.html\" target=\"_blank\" rel=\"noopener\">Toxoplasmosis<\/a> in otherwise healthy people produces only mild symptoms but can be serious in immunocompromised people and to <a href=\"https:\/\/theconversation.com\/toxoplasma-is-a-common-parasite-that-causes-birth-defects-but-the-us-doesnt-screen-for-it-during-pregnancy-232936\" target=\"_blank\" rel=\"noopener\">gestating fetusus<\/a>.<\/p>\n\n<p>Unlike most pathogens, <em>Toxoplasma<\/em> can cross the blood-brain barrier and invade brain cells. Once inside neurons, the parasite releases a suite of proteins that <a href=\"https:\/\/doi.org\/10.1128\/cmr.00005-17\" target=\"_blank\" rel=\"noopener\">alter gene expression in its host<\/a>, which may be a factor in the <a href=\"https:\/\/doi.org\/10.1016\/j.neubiorev.2018.11.012\" target=\"_blank\" rel=\"noopener\">behavioral changes<\/a> it causes in infected animals and people.<\/p>\n\n<figure>\n            <iframe loading=\"lazy\" width=\"440\" height=\"260\" src=\"https:\/\/www.youtube.com\/embed\/M9VoVho5p3k?wmode=transparent&amp;start=0\" frameborder=\"0\" allowfullscreen=\"\"><\/iframe>\n            <figcaption><span class=\"caption\">Scientists retooled <em>Toxoplasma<\/em> to deliver drugs to neurons.<\/span><\/figcaption>\n          <\/figure>\n\n<p>In a new study, a global team of researchers <a href=\"https:\/\/doi.org\/10.1038\/s41564-024-01750-6\" target=\"_blank\" rel=\"noopener\">hijacked the system <em>Toxoplasma<\/em> uses<\/a> to secrete proteins into its host cell. The team genetically engineered <em>Toxoplasma<\/em> to make a hybrid protein, fusing one of its secreted proteins to a <a href=\"https:\/\/medlineplus.gov\/genetics\/gene\/mecp2\/\" target=\"_blank\" rel=\"noopener\">protein called MeCP2<\/a>, which regulates gene activity in the brain \u2013 in effect, giving the MeCP2 a piggyback ride into neurons. Researchers found that the parasites secreted the MeCP2 protein hybrid into neurons grown in a petri dish as well as in the brains of infected mice.<\/p>\n\n<p>A genetic deficiency in MECP2 causes a rare brain development disorder called <a href=\"https:\/\/www.mayoclinic.org\/diseases-conditions\/rett-syndrome\/symptoms-causes\/syc-20377227\" target=\"_blank\" rel=\"noopener\">Rett syndrome<\/a>. Gene therapy trials <a href=\"https:\/\/www.rettsyndrome.org\/clinical-trial-news-updates\/\" target=\"_blank\" rel=\"noopener\">using viruses to deliver the MeCP2 protein<\/a> to treat Rett syndrome are underway. If <em>Toxoplasma<\/em> can deliver a form of MeCP2 protein into brain cells, it may provide another option to treat this currently incurable condition. It also may offer another treatment option for other neurological problems that arise from errant proteins, <a href=\"https:\/\/theconversation.com\/alzheimers-disease-is-partly-genetic-studying-the-genes-that-delay-decline-in-some-may-lead-to-treatments-for-all-205914\" target=\"_blank\" rel=\"noopener\">such as Alzheimer\u2019s<\/a> and <a href=\"https:\/\/theconversation.com\/newly-discovered-genetic-variant-that-causes-parkinsons-disease-clarifies-why-the-condition-develops-and-how-to-halt-it-226435\" target=\"_blank\" rel=\"noopener\">Parkinson\u2019s disease<\/a>.<\/p>\n\n<h2 id=\"the-long-road-ahead\">The long road ahead<\/h2>\n\n<p>The <a href=\"https:\/\/theconversation.com\/tenacious-curiosity-in-the-lab-can-lead-to-a-nobel-prize-mrna-research-exemplifies-the-unpredictable-value-of-basic-scientific-research-214770\" target=\"_blank\" rel=\"noopener\">road from laboratory bench to bedside<\/a> is long and filled with obstacles, so don\u2019t expect to see engineered <em>Toxoplasma<\/em> in the clinic anytime soon.<\/p>\n\n<p>The obvious complication in using <em>Toxoplasma<\/em> for medical purposes is that it can produce a serious, lifelong infection that is currently incurable. Infecting someone with <em>Toxoplasma<\/em> can <a href=\"https:\/\/www.cdc.gov\/toxoplasmosis\/about\/index.html\" target=\"_blank\" rel=\"noopener\">damage critical organ systems<\/a>, including the brain, eyes and heart.<\/p>\n\n\n\n<p>However, up to <a href=\"https:\/\/doi.org\/10.1111\/j.1550-7408.2008.00345.x\" target=\"_blank\" rel=\"noopener\">one-third of people worldwide<\/a> currently carry <em>Toxoplasma<\/em> in their brain, apparently without incident. Emerging studies have correlated infection with increased risk of schizophrenia, rage disorder and recklessness, hinting that this quiet infection may be <a href=\"https:\/\/doi.org\/10.1155%2F2021%2F6634807\" target=\"_blank\" rel=\"noopener\">predisposing some people to serious neurological problems<\/a>.<\/p>\n\n<p>The widespread prevalence of <em>Toxoplasma<\/em> infections may also be another complication, as it disqualifies many people from using it for treatment. Since the billions of people who already carry the parasite have developed immunity against future infection, therapeutic forms of <em>Toxoplasma<\/em> would be rapidly destroyed by their immune systems once injected.<\/p>\n\n<p>In some cases, the benefits of using <em>Toxoplasma<\/em> as a drug delivery system may outweigh the risks. Engineering benign forms of this parasite could produce the proteins patients need without harming the organ \u2013 the brain \u2013 that defines who we are.<!-- Below is The Conversation's page counter tag. Please DO NOT REMOVE. --><img  loading=\"lazy\"  decoding=\"async\"  src=\"data:image\/png;base64,iVBORw0KGgoAAAANSUhEUgAAAAEAAAABAQMAAAAl21bKAAAAA1BMVEUAAP+KeNJXAAAAAXRSTlMAQObYZgAAAAlwSFlzAAAOxAAADsQBlSsOGwAAAApJREFUCNdjYAAAAAIAAeIhvDMAAAAASUVORK5CYII=\"  alt=\"The Conversation\"  width=\"1\"  height=\"1\"  style=\"border: none !important; box-shadow: none !important; margin: 0 !important; max-height: 1px !important; max-width: 1px !important; min-height: 1px !important; min-width: 1px !important; opacity: 0 !important; outline: none !important; padding: 0 !important\"  referrerpolicy=\"no-referrer-when-downgrade\"  class=\" pk-lazyload\"  data-pk-sizes=\"auto\"  data-pk-src=\"https:\/\/counter.theconversation.com\/content\/235928\/count.gif?distributor=republish-lightbox-basic\" ><!-- End of code. If you don't see any code above, please get new code from the Advanced tab after you click the republish button. The page counter does not collect any personal data. More info: https:\/\/theconversation.com\/republishing-guidelines --><\/p>\n\n  <p><span><a href=\"https:\/\/theconversation.com\/profiles\/bill-sullivan-703249\" target=\"_blank\" rel=\"noopener\">Bill Sullivan<\/a>, Professor of Pharmacology and Toxicology, <em><a href=\"https:\/\/theconversation.com\/institutions\/indiana-university-1368\" target=\"_blank\" rel=\"noopener\">Indiana University<\/a><\/em><\/span><\/p>\n\n  <p>This article is republished from <a href=\"https:\/\/theconversation.com\" target=\"_blank\" rel=\"noopener\">The Conversation<\/a> under a Creative Commons license. Read the <a href=\"https:\/\/theconversation.com\/a-common-parasite-could-one-day-deliver-drugs-to-the-brain-how-scientists-are-turning-toxoplasma-gondii-from-foe-into-friend-235928\" target=\"_blank\" rel=\"noopener\">original article<\/a>.<\/p>\n<\/div>\n\n","protected":false},"excerpt":{"rendered":"Toxoplasma is often transmitted to people from contaminated food or cat feces. Dr_Microbe\/iStock via Getty Images Plus Bill&hellip;\n","protected":false},"author":912,"featured_media":12459,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"nf_dc_page":"","fifu_image_url":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/b\/b5\/T._gondii_tachyzoites.jpg\/2560px-T._gondii_tachyzoites.jpg","fifu_image_alt":"","footnotes":""},"categories":[15,12,11],"tags":[626,474,1562],"class_list":{"0":"post-12457","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-engineering","8":"category-health-and-body","9":"category-nature","10":"tag-genetic-engineering","11":"tag-the-conversation","12":"tag-toxoplasma","13":"cs-entry","14":"cs-video-wrap"},"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/posts\/12457","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/users\/912"}],"replies":[{"embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/comments?post=12457"}],"version-history":[{"count":1,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/posts\/12457\/revisions"}],"predecessor-version":[{"id":12458,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/posts\/12457\/revisions\/12458"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/media\/12459"}],"wp:attachment":[{"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/media?parent=12457"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/categories?post=12457"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/tags?post=12457"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}