This is a recurring column on early-stage research in animals or other laboratory models that has not entered the clinic yet but could have implications for future research and development of human medicines.
Targeting chronic itch at the spinal cord
Researchers have identified a receptor on the spinal cord of mice that could be targeted to stop chronic itch, which affects millions of people and occurs in many medical conditions and as a result of some medication.
Researchers led by Mark Hoon from the U.S. National Institutes of Health's National Institute of Dental and Craniofacial Research identified a molecule called Nppb that drives itching in mice. Because Nppb can be found throughout the body and shutting it down with drugs may not be safe, the scientists identified a receptor called NPR1, which is only found on the spinal cord.
In collaboration with the NIH's National Center for Advancing Translational Sciences, Hoon and James Inglese screened more than 85,000 compounds for potential use in blocking NPR1 and therefore the itch. The initial screen yielded more than 1,400 compounds that could potentially serve as inhibitors of NPR1, which they whittled down to 15 and tested on models of mouse itch. The results were published in Science Translational Medicine.
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One of the 15 compounds was selected for further safety studies and showed a brief drop in blood pressure immediately after the mouse received the injection, although this returned to normal within five minutes. No other unwanted effects were observed on behavior or movement, and the mice were then exposed to histamine to provoke itch. Scratching responses were more than halved in the mice that had been exposed to the experimental compound, and it also reduced scratching in mice with a chronic itch condition, although skin inflammation itself was not reduced.
Furthermore, the scientists discovered that the dorsal root ganglia, which carries information to the spinal cord in humans, contains similar amounts of Nppb to those observed in mice and NPR1 is also found in similar amounts in humans as mouse spinal cord tissue.
"We've shown that blocking NRP1 could be a potential approach to treating chronic itch," said Inglese. "Additional studies are needed to identify and refine a drug that could be safely tested in people."
Stuttering gene mutation unearthed
Like King George the VI, the reluctant and stammering English King whose life was immortalized in the film "The King's Speech," a quarter of children who stutter will continue to have their natural flow of speech involuntarily interrupted for life. But U.S. researchers looking at problems with brain circuits that control speech have identified mutations in genes linked to stuttering, which play a role in intracellular trafficking — the process of transporting substances needed for functioning around the cell.
Scientists led by Dennis Drayna at the U.S. NIH's National Institute on Deafness and Other Communication Disorders, or NIDCD, genetically engineered mice with a mutation in one of these previously identified mouse genes in order to identify changes in the brain brought about by mutations in these genes. Results of the study — which was carried out in conjunction with researchers from the National Institute of Mental Health and the National Heart, Lung, and Blood Institute — were published in Proceedings of the National Academy of Sciences.
They discovered that mice with the Gnptab mutations had unusually long pauses in their vocalization and fewer brain cells known as astrocytes, which play a critical role in supporting nerve cells.
"The identification of genetic, molecular, and cellular changes that underlie stuttering has led us to understand persistent stuttering as a brain disorder," said Andrew Griffith, science director at the NIDCD. "Perhaps even more importantly, pinpointing the brain region and cells that are involved opens opportunities for novel intervention for stuttering — and possibly other speech disorders."
Tracking Parkinson's proteins from gut to brain
Researchers have been able to track the spread of a protein thought to be responsible for Parkinson's disease from the gut to the brain by following the vagus nerve, which connects the brain to the body, in studies carried out on mice.
Researchers at Johns Hopkins University injected mice with a type of protein called alpha-synuclein to test if it might misfold and first accumulate in the gut, before tracking it to see if it progressed to the brain. Led by Ted Dawson and Hanseok Ko, they found that the misfolded protein slowly spread to regions of the mouse brain associated with Parkinson's disease. The injected mice performed worse on movement, strength, dexterity and memory tests compared with mice that had not been injected.
Published in the journal Neuron, the scientists' studies also found that interfering with the chain reaction caused by the misfolded protein stopped the spread of alpha-synuclein from gut to brain.
"These findings provide further proof of the gut's role in Parkinson's disease, and gives us a model to study the disease's progression from the start," Dawson said. Blocking the transmission of alpha-synuclein from gut to brain "presents a target for early intervention in the disease."

Scientists are testing a receptor on the spine of mice that could lead to a treatment for chronic itch.