In a new study NYU School of Medicine researchers report that they have found several chemical compounds, including an antidepressant, that have powerful effects against brain-destroying prion infections in mice, opening the door to potential treatments for human prion diseases.
The researchers, led by Thomas Wisniewski, MD, professor of neurology, pathology and psychiatry, report their findings in today's online edition of PLoS One. Prion diseases are a family of rare progressive neurodegenerative disorders that affect both humans and animals. An unusual infectious agent, a prion—a misshapen version of a normal cellular protein—causes the fatal disorders. There are no treatments.
The researchers found that trimipramine, an antidepressant, and fluphenazine, an antipsychotic, have activity against prions. Since the drugs are already in clinical use, Dr. Wisniewski believes that doctors can test them in human patients with Creutzfeldt-Jakob disease, the most common human prion disease.
Dr. Wisniewski and his colleagues previously found 68 chemical compounds, known as styryl-based compounds, bound tightly to amyloid-beta protein deposits in the brains of people who died of Alzheimer's disease. Since the disease-causing aggregates of amyloid-beta and prion proteins are widely believed to have similar structures, his team screened these 68 styryl-based compounds for their ability to inhibit prion infection in a standard cell culture. They found two that seemed both effective and non-toxic, and confirmed their effectiveness by showing that on average they markedly delayed the onset of symptoms in prion-injected lab mice. The styryl-based compounds also reduced the signs of disease in the mouse brains.
Dr. Wisniewski's team found similar results the antidepressant trimipramine and the anti-schizophrenia drug fluphenazine. Both are chemically related to the anti-protozoal drug quinacrine, which is known to slow prion infection in cell cultures, although it fails to protect prion-infected mice or humans. Their chemical differences from quinacrine apparently enable the two drugs to bind more tightly to toxic prion aggregates, and–like the styryl-based compounds–prevent these aggregates from assembling new copies of themselves.
"One of the trimipramine-treated mice stayed healthy throughout the 400-day study," Dr. Wisniewski says.
The National Institutes of Health funds Dr. Wisniewski's laboratory's work to develop potential prion-disease vaccines. Prion diseases in animals have been known to jump to the human population. A prion disease known as bovine spongiform encephalopathy (BSE, also known as "mad cow disease") swept through cattle in Britain in the 1980s, infected humans via beef products, and killed more than 200 people worldwide.
Currently a prion disease known as chronic wasting disease (CWD) is spreading through the deer and elk population of North America. Humans are increasingly exposed to CWD, for example by eating venison, and although CWD so far doesn't seem transmissible to humans, it has been shown to infect other primates. Dr. Wisniewski and colleagues are testing an oral vaccine for CWD in deer and elk in Colorado.
About NYU Langone Medical Center
NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation's premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world's first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center's tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research. For more information, go to www.NYULMC.org.
Christopher Rucas | EurekAlert!
NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University
How to turn white fat brown
07.12.2016 | University of Pennsylvania School of Medicine
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine