Potential Zika Virus Therapies Identified.
Scientists have identified several potential therapies for the Zika virus from among 6,000 drugs already commercially available or undergoing clinical trials, according to a new study. The research, published Monday in the journal Nature Medicine, could help quicken discovery of medications for Zika and help prevent the neurological disorders associated with it, including microcephaly, a condition in which babies are born with abnormally small heads associated with improper brain development. The new paper identifies about a dozen substances, including a long-used treatment for worm infections, that suppress the pathogen’s replication. Another molecule, currently in clinical trials for liver disease, prevents brain cells in a dish from dying following Zika exposure, a potentially important result given the fetal-brain defects associated with the virus. The study also suggests combinations of these two classes of compounds could be the most effective way to treat Zika.
Simply preventing cell death could lead to chronic infection, so it is also important to keep the virus from spawning, said Mariano Garcia-Blanco, a virologist at the University of Texas Medical Branch in Galveston. He wasn’t involved with the research. Commercial drugs are rarely tested on pregnant women, so it is unknown if the new results would help mothers and their fetuses directly, experts said. “For drug development, pregnancy is a very dangerous place people don’t touch,” said Hongjun Song, a neuroscientist at Johns Hopkins University School of Medicine in Baltimore and one of the lead authors on the study. “Here, we don’t really have a choice. We have a jump-start, [but]…there’s a lot more to do.” The team tested drug candidates in stem cells and so-called brain organoids, mini reconstructions of the developing brain. They will need to validate their findings in animal models and ultimately people. Apart from niclosamide, the worm-killing medication, it is unlikely the molecules shown to halt viral replication would be approved for pregnant women because of potential toxic effects on the fetus. But, virologists said, treating men and nonpregnant women could decrease a pregnant woman’s risk of infection by reducing the amount of virus circulating in people around them. The work is part of a recent trend known as drug repurposing. Rather than engineer compounds from scratch, scientists sift through multitudes of already existing ones to see if any can treat a particular disease. This approach “is particularly useful for urgent [situations],” like the Zika epidemic, during which scientists don’t have time to undergo the lengthy drug-discovery process, said Wei Zheng, a researcher at the National Institutes of Health’s National Center for Advancing Translational Sciences and one of the study’s lead authors.
To move the research forward, the team will begin conducting animal studies shortly, according to Dr. Zheng. They will also test another 80,000 compounds with the help of robots, according to an NIH spokesman. The researchers have filed a patent covering the new findings. The goal is to incite companies to commercialize the research and develop Zika-busting drugs, said the NIH spokesman. Pharmaceutical company Spotlight Innovation Inc. will fund some of the research team’s future work through a partnership with Florida State University’s Hengli Tang, another of the study’s lead authors, according to Geoffrey Laff, Spotlight’s senior vice president of business development. The financial details weren’t disclosed, but amount to “several years of funding,” Dr. Laff said. Spotlight would license any resulting intellectual property, he added. The licensing may get complicated if the results involving liver-disease drug emricasan hold up, and comparable alternatives aren’t found. The compound prevented cell death most potently among molecules tested in the study. Conatus Pharmaceuticals Inc. has several patents for emricasan. Some don’t expire until 2028. A third party wanting to sell the molecule would need to license it from Conatus, according to Joseph O’Malley, global chair for intellectual property at Paul Hastings LLP. “Assuming that drug were to be found to treat Zika,” Mr. O’Malley said, “it would be bad news for the company. It would be under tremendous pressure to license it for little or no money.” Alfred Spada, Conatus’s chief scientific officer, said if emricasan “were effective in the treatment of such a devastating disease, I think we would be ecstatic.”
Credit: Daniela Hernandez for The Wall Street Journal 29 August 2016