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
Christopher Rucas | Newswise Science News
Reptile vocalization is surprisingly flexible
30.05.2017 | Max-Planck-Institut für Ornithologie
New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
30.05.2017 | Life Sciences
30.05.2017 | Power and Electrical Engineering
29.05.2017 | Earth Sciences