Quicknotes

From the Winter 2016 edition of Vanderbilt Medicine Magazine

Compound developed at VUMC may delay Huntington’s disease 

A compound developed by researchers at Vanderbilt University can improve early symptoms and delay progression of Huntington’s disease in a mouse model of the neurodegenerative disorder.

The findings, reported in the Proceedings of the National  Academy of Sciences, offer one  of the first glimmers of hope for  a way to treat the rare genetic disease, which killed folk singer Woody Guthrie in 1967 at age 55.

“We are very excited by the results  of this study,” said P. Jeffrey Conn, Ph.D., director of the Vanderbilt Center for Neuroscience Drug Discovery and lead investigator on the study.

A type of muscarinic acetylcholine receptor called M4, which binds the neurotransmitter acetylcholine, can block these signals. Researchers reasoned that selective activation of M4, therefore, should normalize excessive transmission caused by Huntington’s disease.

Using a compound called a  positive allosteric modulator or PAM, which—like the dimmer switch in an electrical circuit— can turn up the activity of M4,  the researchers showed that they  could completely counteract early deficits in neuronal transmission  in a mouse model of the disease.

 

 

Study explores nicotine patch to treat memory loss 

Can a nicotine patch improve memory loss in older adults with mild cognitive impairment (MCI)?

Vanderbilt has received a $9.4  million grant from the National  Institute on Aging (NIA) to find out.  About 300 older individuals with MCI will be enrolled at about 20 different sites around the country  in the two-year Memory Improvement through Nicotine Dosing study— the largest study of a nicotine patch in non-smokers.

MCI affects millions of people around the world and is the stage between normal aging and dementia when others begin to notice that an individual is developing mild memory or thinking problems. Most people with MCI (about 75 percent) go on to develop Alzheimer’s disease.

Nicotine, a natural plant alkaloid,  is a “fascinating drug with interesting properties,” said Paul Newhouse, M.D., professor of Psychiatry.

“People think of it as a potentially noxious substance, but it’s a plant-derived medication just like a lot of other medications.”

Nicotine binds to very specific  receptors in the brain that are  important for thinking and memory and may have neuroprotective  effects. People with Alzheimer’s disease are known to lose some  of those receptors.

“We’re excited about this study, and to see whether it can change the course of illness in these patients,” Newhouse said. “It’s the essence of repurposing an old drug for a new use.”

 

 

Vitamin C protects blood vessel lining

The endothelial cells lining blood vessels form a tight barrier, which is weakened (permeabilized) by inflammation. Vitamin C tightens the endothelial barrier and maintains  its integrity during inflammation, but the mechanisms for vitamin C action remain unclear.

James May, M.D., and colleagues explored whether and how vitamin C can stabilize the endothelial barrier using human umbilical vein endothelial cells. They reported in the Aug. 28, 2015, issue of the  Journal of Biological Chemistry  that vitamin C prevented increased permeability induced by thrombin, an inflammatory stimulus.

 

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