Researchers at Vanderbilt University Medical Center and Washington University School of Medicine in St. Louis have isolated a human monoclonal antibody that in a mouse model “markedly reduced” infection by the Zika virus.
The antibody, called ZIKV-117, also protected the fetus in pregnant mice infected with the virus, the researchers reported today in the journal Nature. Zika is believed to cause microcephaly, unusually small heads, and other congenital malformations in children born to infected women.
Similar protection studies in primates are warranted, and if the findings hold up, ZIKV-177 could be developed as a protective antibody treatment for pregnant women at risk of Zika infection, the researchers concluded.
The findings may also aid efforts to develop an effective anti-Zika vaccine, said James Crowe Jr., M.D., director of the Vanderbilt Vaccine Center and co-corresponding author of the paper with Michael S. Diamond, M.D., Ph.D., at Washington University.
“These naturally occurring human antibodies isolated from humans represent the first medical intervention that prevents Zika infection and damage to fetuses,” said Crowe, who also is Ann Scott Carell Professor in the Departments of Pediatrics and Pathology, Microbiology & Immunology in the Vanderbilt University School of Medicine.
“We’re excited because the data suggests we may have antibody treatments in hand that could be developed for use in pregnant women,” he said.
“The remarkable potency and breadth of inhibition by ZIKV-117 has great promise,” Diamond said, “as it was able to inhibit infection by strains from both Africa and America in cell culture and in animals, including during pregnancy.”
Diamond is associate director of The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs at Washington University.
Zika is a mosquito-borne virus that has emerged as a global public health threat. In addition to its association with congenital birth defects, Zika has been linked to Guillain-Barre syndrome, a neurological disorder that can lead to paralysis and death.
Since a major outbreak was reported in Brazil last year, Zika infections transmitted by mosquitoes have been reported throughout Africa, Asia, the Pacific, and the Americas, including Miami-Dade County, Florida.
During the past 15 years, Crowe and his colleagues have developed a high-efficiency method for isolating human monoclonal antibodies that can neutralize a wide range of viruses, from Ebola to HIV.
The Crowe and Diamond laboratories have collaborated recently on several projects including the generation of protective human monoclonal antibodies against Dengue, West Nile, Chikungunya and now Zika viruses.
Monoclonal antibodies are made from a single clone of B cells, a type of white blood cell, that have been fused to myeloma (cancer) cells to form fast-growing “hybridomas.” This allows researchers to quickly generate large quantities of antibodies against specific viral targets.
In the current study, the researchers isolated antibodies from the blood of people who’d been previously infected with the Zika virus in different parts of the world. The antibodies reacted to the envelope or “E” protein on the surface of the virus.
The researchers then generated a variety of monoclonal antibodies. In cell culture studies, they identified one, ZIKV-117, which broadly neutralized several different strains of the virus. In mice infected by the Zika virus, injection of the antibody markedly reduced disease and mortality, and reduced transmission from mother to fetus.
Safety of NMN being tested in small clinical trial in Japan
Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells’ ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency in the body’s energy supply chain is a key driver of the aging process.
Now, scientists at Washington University School of Medicine in St. Louis have shown that supplementing healthy mice with a natural compound called NMN can compensate for this loss of energy production, reducing typical signs of aging such as gradual weight gain, loss of insulin sensitivity and declines in physical activity.
The study is published Oct. 27 in the journal Cell Metabolism.
“We have shown a way to slow the physiologic decline that we see in aging mice,” said Shin-ichiro Imai, MD, PhD, a professor of developmental biology and of medicine. “This means older mice have metabolism and energy levels resembling that of younger mice. Since human cells rely on this same energy production process, we are hopeful this will translate into a method to help people remain healthier as they age.”
Imai is working with researchers conducting a clinical trial to test the safety of NMN in healthy people. The phase 1 trial began earlier this year at Keio University School of Medicine in Tokyo.
With age, the body loses its capacity to make a key element of energy production called NAD (nicotinamide adenine dinucleotide). Past work by Imai and co-senior author Jun Yoshino, MD, PhD, an assistant professor of medicine, has shown that NAD levels decrease in multiple tissues as mice age. Past research also has shown that NAD is not effective when given directly to mice so the researchers sought an indirect method to boost its levels. To do so, they only had to look one step earlier in the NAD supply chain to a compound called NMN (nicotinamide mononucleotide).
NMN can be given safely to mice and is found naturally in a number of foods, including broccoli, cabbage, cucumber, edamame and avocado. The new study shows that when NMN is dissolved in drinking water and given to mice, it appears in the bloodstream in less than three minutes. Importantly, the researchers also found that NMN in the blood is quickly converted to NAD in multiple tissues.
“We wanted to make sure that when we give NMN through drinking water, it actually goes into the blood circulation and into tissues,” Imai said. “Our data show that NMN absorption happens very rapidly.”
To determine the long-term effects of giving NMN, Imai, Yoshino and their colleagues studied three groups of healthy male mice fed regular mouse chow diets. Starting at five months of age, one group received a high dose of NMN-supplemented drinking water, another group received a low dose of the NMN drinking water, and a third group served as a control, receiving no NMN. The researchers compared multiple aspects of physiology between the groups, first at 5 months of age and then every three months, until the mice reached 17 months of age. Typical laboratory mice live about two years.
The researchers found a variety of beneficial effects of NMN supplementation, including in skeletal muscle, liver function, bone density, eye function, insulin sensitivity, immune function, body weight and physical activity levels. But these benefits were seen exclusively in older mice.
“When we give NMN to the young mice, they do not become healthier young mice,” Yoshino said. “NMN supplementation has no effect in the young mice because they are still making plenty of their own NMN. We suspect that the increase in inflammation that happens with aging reduces the body’s ability to make NMN and, by extension, NAD.”
In skeletal muscle, the investigators — including the study’s first author, Kathryn Mills, the research supervisor in Imai’s lab — found that NMN administration helps energy metabolism by improving the function of mitochondria, which operate as cellular power plants. They also found that mice given NMN gained less weight with aging even as they consumed more food, likely because their boosted metabolism generated more energy for physical activity. The researchers also found better function of the mouse retina with NMN supplementation, as well as increased tear production, which is often lost with aging. They also found improved insulin sensitivity in the older mice receiving NMN, and this difference remained significant even when they corrected for differences in body weight.
In a paper published earlier this year in Cell Reports, Yoshino and his colleagues revealed more details of how NAD works in influencing glucose metabolism and the body’s fat tissue. In that study, the mice had a defect in the ability to manufacture NAD only in the body’s fat tissue. The rest of their tissues and organs were normal.
“Even though NAD synthesis was stopped only in the fat tissue, we saw metabolic dysfunction throughout the body, including the skeletal muscle, the heart muscle, the liver and in measures of the blood lipids,” Yoshino said. “When we gave NMN to these mice, these dysfunctions were reversed. That means NAD in adipose tissue is a critical regulator of whole body metabolism.”
Added Imai, “This is important because Jun showed that if you mess up NAD synthesis only in fat tissue, you see insulin resistance everywhere. Adipose tissue must be doing something remarkable to control whole body insulin sensitivity.”
During the long-term NMN study in healthy mice, Imai also said they monitored the animals for any potential increase in cancer development as a result of NMN administration.
“Some tumor cells are known to have a higher capability to synthesize NAD, so we were concerned that giving NMN might increase cancer incidence,” Imai said. “But we have not seen any differences in cancer rates between the groups.”
The phase 1 trial in Japan is using NMN manufactured by Oriental Yeast Co., which also provided the NMN used in these mouse studies. Outside of this clinical trial, high-grade NMN for human consumption is not commercially available. But there’s always broccoli.
Dirty to drinkable
Graphene oxide has been hailed as a veritable wonder material; when incorporated into nanocellulose foam, the lab-created substance is light, strong and flexible, conducting heat and electricity quickly and efficiently.
Now, a team of engineers at Washington University in St. Louis has found a way to use graphene oxide sheets to transform dirty water into drinking water, and it could be a global game-changer.
“We hope that for countries where there is ample sunlight, such as India, you’ll be able to take some dirty water, evaporate it using our material, and collect fresh water,” said Srikanth Singamaneni, associate professor of mechanical engineering and materials science at the School of Engineering & Applied Science.
Washington University in St. Louis (Wash. U., or WUSTL) is a private research university located in suburban St. Louis, Missouri, United States.
Founded in 1853, and named after George Washington, the university has students and faculty from all 50 U.S. states and more than 120 countries. Twenty-two Nobel laureates have been affiliated with Washington University, nine having done the major part of their pioneering research at the university. Washington University’s undergraduate program is ranked 14th in the nation and 7th in admissions selectivity by U.S. News and World Report. The university is ranked 30th in the world by the Academic Ranking of World Universities. In 2006, the university received $434 million in federal research funds, ranking seventh among private universities receiving federal research and development support, and in the top four in funding from the National Institutes of Health.
Washington University is made up of seven graduate and undergraduate schools that encompass a broad range of academic fields. Officially incorporated as “The Washington University,” the university is occasionally referred to as “WUSTL,” an acronym derived from its initials. More commonly, however, students refer to the university as “Wash. U.” To prevent confusion over its location, the Board of Trustees added the phrase “in St. Louis” in 1976.
The Latest Updated Research News:
Washington University in St. Louis research articles from Innovation Toronto
- Engineers develop novel hybrid nanomaterials to transform water purification – July 27, 2016
- Grow a living hip replacement and fight arthritis as well – July 21, 2016
- Engineers to use cyborg insects as biorobotic sensing machines – June 29, 2016
- As more states legalize marijuana, adolescents’ problems with pot decline – May 26, 2016
- Stem cells from diabetic patients coaxed to become insulin-secreting cells – May 12, 2016
- Nanoparticles present sustainable way to grow food crops with less phosphorus – April 30, 2016
- Novel nanoparticle made of common mineral may help keep tumor growth at bay – February 4, 2016
- Tomatoes get boost in growth, antioxidants from nano-sized nutrients – November 8, 2015
- Eye Drops Could Clear Up Cataracts Using Newly Identified Chemical – November 5, 2015
- Smart cornfields of the future – July 18, 2015
- Discovery Of Vulnerability In Brain Tumor Stem Cells May Lead To Successful Brain Cancer Treatment – June 14, 2015
- Device Developed at WashU May Allow Sensations in Prosthetic Hands – May 14, 2015
- Light — not pain-killing drugs — used to activate brain’s opioid receptors – May 1, 2015
- World’s fastest 2-D camera may enable new scientific discoveries – December 6, 2014
- Human skin cells reprogrammed directly into brain cells – October 26, 2014
- Plasmonic Paper – October 13, 2014
- The Dwindling Stock of Antibiotics, and What to Do About It- October 11, 2014
- New Hand-Held Device Uses Lasers, Sound Waves for Deeper Melanoma Imaging – August 8, 2014
- A protein key to the next Green Revolution sits for its portrait – May 3, 2014
- Copper nanowires could become basis for new solar cells – April 27, 2014
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- Shining a little light changes metal into semiconductor
- Aging really is ‘in your head’
- How Surveillance Changes Behavior: A Restaurant Workers Case Study
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- The dangers of surveillance – it’s bad, but why?
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- Company Unveils DNA Sequencing Device Meant to Be Portable, Disposable and Cheap
- Novel Metal Catalysts May Be Able to Turn Greenhouse Gases Into Liquid Fuels
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Technique uses 3-D weaving to grow a living hip replacement
With a goal of treating worn, arthritic hips without extensive surgery to replace them, scientists have programmed stem cells to grow new cartilage on a 3-D template shaped like the ball of a hip joint. What’s more, using gene therapy, they have activated the new cartilage to release anti-inflammatory molecules to fend off a return of arthritis.
The technique, demonstrated in a collaborative effort between Washington University School of Medicine in St. Louis and Cytex Therapeutics Inc. in Durham, N.C., is described July 18 in Proceedings of the National Academy of Sciences.
The discovery one day may provide an alternative to hip-replacement surgery, particularly in younger patients. Doctors are reluctant to perform such operations in patients under age 50 because prosthetic joints typically last for less than 20 years. A second joint-replacement surgery to remove a worn prosthetic can destroy bone and put patients at risk for infection.
“Replacing a failed prosthetic joint is a difficult surgery,” said Farshid Guilak, PhD, a professor of orthopedic surgery at Washington University. “We’ve developed a way to resurface an arthritic joint using a patient’s own stem cells to grow new cartilage, combined with gene therapy to release anti-inflammatory molecules to keep arthritis at bay. Our hope is to prevent, or at least delay, a standard metal and plastic prosthetic joint replacement.”
A team of engineers from Washington University in St. Louis is looking to capitalize on the sense of smell in locusts to create new biorobotic sensing systems that could be used in homeland security applications.
Baranidharan Raman, associate professor of biomedical engineering in the School of Engineering & Applied Science, has received a three-year, $750,000 grant from the Office of Naval Research (ONR) to use the highly sensitive locust olfactory system as the basis to develop a bio-hybrid nose. Joining Raman in the research are engineering colleagues Srikanth Singamaneni, associate professor of materials science, and Shantanu Chakrabartty, professor of computer science & engineering.
Biological sensing systems are far more complex than their engineered counterparts, including the chemical sensing system responsible for our sense of smell, Raman said. Although the sense of smell is a primitive sense, it is conserved across many vertebrate and invertebrate species.
“It appears that biology converged onto a solution for the problem of non-invasive, or ‘standoff’ chemical sensing and has replicated the same design and computing principles everywhere,” Raman said. “Therefore, understanding the fundamental olfactory processing principle is necessary to engineer solutions inspired by biology.”
For several years and with prior funding from the ONR, Raman has been studying how sensory signals are received and processed in relatively simple brains of locusts. He and his team have found that odors prompt dynamic neural activity in the brain that allow the locust to correctly identify a particular odor, even with other odors present. In other research, his team also has found that locusts trained to recognize certain odors can do so even when the trained odor was presented in complex situations, such as overlapping with other scents or in different background conditions.
“Why reinvent the wheel? Why not take advantage of the biological solution?”
Compound Restores Transparency to Mouse Lenses, Human Lens Tissue
Through these experiments, said Gestwicki, “We are starting to understand the mechanism in detail. We know where compound 29 binds, and we are beginning to know exactly what it’s doing.” The team next tested compound 29 in an eye-drop formulation in mice carrying mutations that make them predisposed to cataracts.
Similar results were seen when compound 29 eye drops were applied in mice that naturally developed age-related cataracts, and also when the compound was applied to human lens tissue affected by cataracts that had been removed during surgery.
He has licensed the compound from U-M and Makley, a former graduate student and postdoctoral fellow in the Gestwicki laboratory, is founder and chief scientific officer of ViewPoint Therapeutics, a company that is actively developing compound 29 for human use.
In addition to compound 29’s potential for cataract treatment, the insights gained through the research could have broader applications, said Gestwicki, a member of UCSF’s Institute for Neurodegenerative Diseases whose main research interest is dementia and related disorders.