At the Virginia Tech Carilion Research Institute, three scientists are planning to create a virus capable of destroying brain cancer. It sounds like the stuff of science fiction, but it isn\u2019t hypothetical \u2013 the researchers were recently awarded a grant from the Commonwealth Research Commercialization Fund, part of the Center for Innovative Technology, to engineer a viral therapy.<\/p>\n
The scientists\u2019 goal is to eradicate glioblastomas, particularly nasty cancerous tumors found in the brain. From the time of diagnosis, the average patient has a year to live. With the current standard of treatment \u2013 including surgery, chemotherapy, and radiation \u2013 a patient might live an extra two months beyond that.<\/p>\n
\u201cElongating a person\u2019s life by two months is huge for a doctor,\u201d said Zhi Sheng, one of the grant recipients and an assistant professor at the Virginia Tech Carilion Research Institute. \u201cFor the patient? It\u2019s not enough.\u201d<\/p>\n
One of the major problems with treating glioblastomas is that it\u2019s nearly impossible to surgically remove every cancerous cell.<\/p>\n
\u201cThese cells hide away in little niches in the brain,\u201d said Robert Gourdie, another grant recipient and the director of the Center for Heart and Regenerative Medicine Research at the Virginia Tech Carilion Research Institute. \u201cYou think you\u2019ve resected the tumor and killed the disease off, and then it springs up somewhere else like whack-a-mole.\u201d<\/p>\n
The obvious answer is to douse the remaining cells with chemotherapy drugs, but glioblastomas are resistant to all but one. The only effective drug available to treat this type of cancer is temozolomide, known as TMZ. Therein lies the other major problem. Glioblastomas make it a point to know their enemy, and the cells quickly become resistant to TMZ as well.<\/p>\n
It takes about 14 years to develop and produce a new drug that may or may not be as efficacious as a currently available pharmaceutical, Sheng said. For glioblastoma patients, that\u2019s far too long to wait. With the new brain cancer virus approach, there is hope for faster solutions.<\/p>\n
\u201cWe can save some time by studying existing drugs and combining them in different ways,\u201d Sheng said. \u201cThat\u2019s why we looked at the ACT1 peptide.\u201d<\/p>\n
ACT1 \u2013 developed in Gourdie\u2019s laboratory at the Medical University of South Carolina before the laboratory relocated to the Virginia Tech Carilion Research Institute \u2013 was designed to enhance electrical communication between cardiac cells. The peptide prevents two proteins \u2013 connexin 43 and ZO1 \u2013 from binding. If those two proteins do bind, it opens the floodgates, allowing the cells\u2019 viscera to escape.<\/p>\n
Gourdie and his team discovered that the peptide also halves healing time of skin ulcers, by preventing the swelling and scar tissue formation that comes with the opened floodgates. Gautam Ghatnekar, Gourdie\u2019s postdoctoral associate at the time, founded FirstString Research, Inc., to further test and develop the peptide\u2019s pharmaceutical uses.<\/p>\n
Recent studies point to connexin 43, one of the proteins that ACT1 targets, as a participant in desensitizing glioblastomas to TMZ. Gourdie and Sheng realized that if the cancer cells were treated with ACT1, they might become sensitive to TMZ again. It would be tricky, since ACT1 is short lived and must be administered frequently to maintain the communication benefits. But if Gourdie and Sheng combined their efforts, they could tackle the disease in a completely novel way.<\/p>\n
\u201cRob\u2019s team had the peptide and my team had a glioblastoma model system,\u201d Sheng said. \u201cWe put ACT1 and TMZ together and found that the combination substantially inhibits the growth of brain cancer virus glioblastoma cells.\u201d<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n
The scientists injected animal glioblastoma model with ACT1, TMZ, or a combination of the two. The tumors that received the combination were significantly smaller, and, in some cases, not visible at all.<\/p>\n
\u201cIt was a striking result,\u201d Gourdie said. \u201cIt was the kind of result that doesn\u2019t come along that often.\u201d<\/p>\n
The preliminary results provided evidence that tumors directly treated with the ACT1\/TMZ combination shrank \u2013 but that was only the first step. Now the researchers need to figure out how to get the peptide consistently to the right place at the right time with the TMZ.<\/p>\n
\u201cWe\u2019re going to try a virus,\u201d Sheng said. \u201cThe virus will deliver DNA to the tumor cells, making them express the ACT1 peptide. Those cells will then become TMZ sensitive and we can kill them.\u201d<\/p>\n
It\u2019s an engineering project at the molecular level. Samy Lamouille, a research assistant professor at the Virginia Tech Carilion Research Institute and the head of discovery at FirstString Research, plans to design a virus capable of carrying ACT1 directly to the glioblastoma cells.<\/p>\n
Viruses operate by infecting cells and introducing genetic material \u2013 they hijack the cell body to do its bidding. To engineer a virus, Lamouille will start with the genetic material. He\u2019ll take a plasmid \u2013 a small molecule of DNA that can replicate \u2013 and splice in new characteristics. One of the first is a genetic sequence that will help the virus target cancer cells by making the virus express a receptor for cytokine interleukin 13, a receptor that is highly expressed in glioblastomas.<\/p>\n
The process will repeat, as Lamouille continues to add pieces to change what the plasmid is capable of doing. Eventually, Lamouille will end up with a virus that will target brain cancer cells and infect them with the genetic ability to express ACT1.<\/p>\n
\u201cIt\u2019s strange to talk about viruses as a way to treat disease, but they can be engineered by us and are efficient at delivering genetic information,\u201d Lamouille said. \u201cWe can design that genetic code to express what we want. It\u2019s an effective treatment.\u201d<\/p>\n
There are no guarantees that the virus will prove the best way to deliver ACT1 to the glioblastoma cells, though. \u201cIn research, it\u2019s good to have a plan B,\u201d Lamouille said. The other option Gourdie, Sheng, and Lamouille are exploring is to use biodegradable material, called a wafer, loaded with the ACT1 and TMZ. It would be placed directly into the brain, after a tumor resection, in the same area. The wafer would release the drugs gradually, treating the leftover cancer cells slowly to destroy the TMZ resistance.<\/p>\n
Once the scientists test the efficacy and safety of the virus and the wafer in the laboratory, they plan to proceed with clinical trials in dogs.<\/p>\n
\u201cDogs get glioblastomas at the same rate as people,\u201d Gourdie said, noting that Professor John Rossmeisl, a veterinary neurosurgeon at the Virginia\u2013Maryland College of Veterinary Medicine, sees 20 to 30 dogs a year with the cancer. \u201cThis might be the best chance for a dog with terminal cancer and, since it would be a clinical trial, the cost of treatment would be covered.\u201d<\/p>\n
The study goes full circle, beyond the benefits of developing a treatment for fatal disease, to the fundamental science that led to the development of ACT1.<\/p>\n
\u201cWe\u2019re not only trying to overcome the therapeutic resistance,\u201d Sheng said. \u201cWe\u2019re also trying to figure out how and why glioblastomas become resistant at the molecular level. We\u2019ve come this far. We know we can do it.\u201d<\/p>\n
Source: Virginia Tech<\/p>\n
Date: January 12, 2015<\/strong><\/p>\n SUBSCRIBE TO OUR BLOG IN THE RIGHT SIDEBAR MENU TO RECEIVE OUR DAILY BLOG POST DIRECTLY TO YOUR E-MAIL<\/span><\/p>\n SUBSCRIBE TO OUR NEWSLETTER TO RECEIVE A MONTHLY MAIL WITH MORE RELEVANT INDUSTRY AND COMPANY NEWS<\/span><\/p>\n","protected":false},"excerpt":{"rendered":" En el Instituto de Investigaci\u00f3n Carilion de Virginia Tech, tres cient\u00edficos planean crear un virus capaz de destruir el c\u00e1ncer cerebral. Parece ciencia ficci\u00f3n, pero no es una hip\u00f3tesis: los investigadores han recibido recientemente una subvenci\u00f3n de...<\/p>","protected":false},"author":3,"featured_media":43298,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[968],"tags":[962,1046,1065],"class_list":["post-3569","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-blogs-updates","tag-neurology","tag-oncology","tag-pharma"],"acf":[],"_links":{"self":[{"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/posts\/3569","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/comments?post=3569"}],"version-history":[{"count":0,"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/posts\/3569\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/media\/43298"}],"wp:attachment":[{"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/media?parent=3569"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/categories?post=3569"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/fomatmedical.com\/es\/wp-json\/wp\/v2\/tags?post=3569"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}