Gene editing reverses Huntington's in mouse model

This is a concrete example, not yet clinical, of what can be done with CRISPR/Cas9 gene Read more

Urine tests for prostate cancer could reduce biopsies

Urine RNA tests could reduce the number of biopsies by giving a preview of a cancer's aggressiveness. Featuring Martin Sanda and Carlos Read more

Mitochondrial blindness -- Newman's Emory story

Neuro-ophthalmologist Nancy Newman’s 2017 Dean’s Distinguished Faculty Lecture and Award were unexpectedly timely. Her talk on Tuesday was a tour of her career and mitochondrial disorders affecting vision, culminating in a description of gene therapy clinical trials for the treatment of Leber’s hereditary optic neuropathy. The sponsor of those studies, Gensight Biologics, recently presented preliminary data on a previous study of their gene therapy at the American Academy of Neurology meeting in April. Two larger trials Read more

Neuro

Alzheimer’s expert weighs in on proposed guidelines

Scans can show beta amyloid, a protein associated with Alzheimer’s disease (right)

For the first time in 25 years, medical experts are proposing new diagnostic criteria aimed at better and earlier detection of Alzheimer’s disease (AD).

The guidelines, proposed by the National Institute on Aging (NIA) and the Alzheimer’s Association, update and revise the current Alzheimer’s criteria with modern technologies and the latest research advances.

According to the Alzheimer’s Association, an estimated 5.3 million Americans have AD, most of them 65 and older. The disease is thought to begin years, possibly even decades, before symptoms are noticeable. But there is no single, generally accepted way to identify the disease in its earliest stages before symptoms are evident.

The new diagnostic guidelines focus on advances in detecting biomarkers for the disease, such as substances found in spinal fluid or appearing on cutting-edge brain imaging scans conducted with PET or MRI.

Emphasis will be on diagnosing early stages of the disease as soon as possible so that patients can take measures to slow the progression or prevent further damage.

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Posted on by Jennifer Johnson in Neuro Leave a comment

Untangling the mysteries of Alzheimer’s disease

Lary Walker, PhD

Consider this: Alzheimer’s is a uniquely human disorder. But why? Why don’t nonhuman primates, such as monkeys, get Alzheimer’s disease. Monkeys form the senile plaques that are identical to the plaques found in humans. So do other animals.

“Yet, despite the fact that nonhuman primates make this protein that we know is very important in the pathogenesis of Alzheimer’s disease, they don’t develop the full disease,” says Lary Walker, PhD. Walker is an associate professor at Yerkes National Primate Research Center.

“They don’t develop the tangles we associate with Alzheimer’s disease, the neuronal loss, the shrinkage of the brain, and they don’t get demented in the sense that humans do,” says Walker.

When our bodies make a protein, the protein tends to fold into a functional form. But when it comes to Alzheimer’s disease, some proteins misfold, becoming sticky and then combining with one another. In their collective form, the proteins can then form plaques or tangles, the two types of lesions associated with Alzheimer’s disease.

And for some unknown reason, people who have plaques usually go on to form tangles. But people who have tangles don’t always go on to form plaques. No one is sure why. But that’s what researcher Walker wants to find out.

To listen to Walker’s own words about Alzheimer’s disease, access Emory’s new Sound Science podcast.

Posted on by Robin Tricoles in Neuro Leave a comment

Study: ADHD linked to pesticide exposure

A study published in the May 17, 2010, issue of the journal Pediatrics found that one type of pesticide commonly used on fruits and vegetables may be contributing to attention deficit hyperactivity disorder, or ADHD, in children.

The study measured the levels of pesticide byproducts in the urine of 1,139 children from across the United States. Children with the highest concentration of pesticides in their urine were more likely to have symptoms of ADHD.

Dana Boyd Barr, PhD, a research professor in the Rollins School of Public Health at Emory, spent more than 20 years studying pesticide exposure at the Centers for Disease Control and Prevention (CDC). Barr was not a member of the research team that published these findings on pesticides and ADHD, but data generated in her former CDC lab was analyzed for this particular study.

Barr says while the study doesn’t prove causality between pesticide exposures and ADHD, it does shed light on how even low level daily exposures to pesticides could potentially impact cognitive health.

“It seems very plausible that low-level daily exposures to pesticides can produce some subtle effects like ADHD or other neurological delays,” she says.

Barr notes that additional research is needed to confirm a connection to pesticides and ADHD, but says there are tips for limiting your exposure to commonly used pesticides.

“We’ve done studies here at Emory and also at CDC that have indicated that if you use organic food or if you wash your food properly prior to preparation, you can reduce the levels of these metabolites in your urine.  Eat as much organic produce as possible, or wash your fruits and vegetables very well and that likely could decrease the chances of your children developing ADHD,” says Barr.

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Quirky little prairie voles hold answers

Larry Young, PhD

So says Larry Young, PhD, chief of the Division of Behavioral Neuroscience and Psychiatric Disorders at the Yerkes National Primate Research Center, Emory University.

Young, who is world-renowned for his work on the role of neuropeptides in regulating social behavior, uses voles to investigate the neurobiological and genetic mechanisms underlying social behavior. Using the monogamous prairie vole (vs. the promiscuous meadow vole) as a model organism, Young and his research team identified the oxytocin and vasopressin receptors as key mediators of social bonding and attachment. In addition, they are examining the consequences of social bond disruption as a model of social loss-induced depression.

This work has important implications for developing novel treatment strategies for psychiatric disorders associated with social cognitive deficits, including autism spectrum disorders and schizophrenia.

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Posted on by Holly Korschun in Neuro Leave a comment

Combined MR/PET imaging

On Thursday, April 8, Emory’s Center for Systems Imaging, directed by Department of Radiology Chair Carolyn Meltzer, MD, and the Atlanta Clinical & Translational Science Institute celebrated the launch of the CSI’s prototype MR/PET imaging scanner.

View of MR/PET

View of MR/PET scanner from front, with Ciprian Catana of MGH and Larry Byars of Siemens

The scanner is one of four world-wide and one of two in the United States, and permits simultaneous MR (magnetic resonance) and PET (positron emission tomography) imaging in human subjects. This provides the advantage of being able to combine the anatomical information from MR with the biochemical/metabolic information from PET. Potential applications include functional brain mapping and the study of neurodegenerative diseases, drug addiction and brain cancer.

Thursday’s event brought together leaders of the three other MR/PET programs in Boston, Jülich and Tübingen, the Siemens engineers who designed the device, and the Atlanta research community to explore the possibilities of the technology.

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Posted on by Quinn Eastman in Neuro Leave a comment

Two birds with one stone in treatment of Alzheimer’s

Allan Levey, MD, PhD

The drugs now available to treat Alzheimer’s address the symptoms of the disease — memory problems — rather than the underlying mechanism of neurodegeneration.

But what if something could do both? Here’s a tantalizing prospect, hinted at by a long-running thread of brain research: compounds that boost the function of certain acetylcholine circuits in the brain might also modify production of toxic beta-amyloid protein.

Emory neurologists Allan Levey and Jim Lah and members of their laboratories have been working on this idea, together with Jeffrey Conn’s group at Vanderbilt, for several years.

James Lah, MD, PhD

The possibility grows out of the properties of certain receptors for the neurotransmitter acetylcholine, called “muscarinic acetylcholine receptors.” Acetylcholine is a major transmitter of signals in the brain, and there are several varieties of receptors, or receiver dishes for the signals, on brain cells.

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Posted on by Quinn Eastman in Neuro Leave a comment

Probing a puzzling form of muscular dystrophy

Two researchers at Emory, Anita Corbett and Grace Pavlath, recently have combined their expertise to probe how a puzzling form of muscular dystrophy develops.

Oculopharyngeal muscular dystrophy (OPMD) is an inherited type of muscular dystrophy that primarily affects muscles of the face and throat. In the video below, Anita Corbett explains how this affects patients as they get older.


The mutations that cause the disease make a protein called PABPN1 longer and stickier than normal, and the mutated protein appears to form clumps in muscle cells.

The puzzle lies in that PABPN1 (poly A binding protein nuclear 1) can be found everywhere in the body, but it’s not clear why the mutated protein specifically affects muscle cells — or why the muscles in the face and throat are especially vulnerable.

In December 2009, Corbett, Pavlath and postdoctoral fellow Luciano Apponi published a paper where they suggest that the clumps of mutated protein, which some researchers have proposed to be toxic, might not be the whole story. A lack of functioning PABPN1 might be just as strong a factor in the disease, they’ve discovered.

The results will appear in a future issue of the journal Human Molecular Genetics.

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Posted on by Quinn Eastman in Neuro Leave a comment

A new class of brain-protecting drugs

Pathologist Keqiang Ye has made a series of discoveries recently, arising from his investigations of substances that can mimic the growth factor BDNF (brain-derived neurotrophic factor).

BDNF is a protein produced by the brain that pushes neurons to withstand stress and make new connections. Some neuroscientists have described BDNF as “Miracle Gro for brain cells.”

“BDNF has been studied extensively for its ability to protect neurons vulnerable to degeneration in several diseases, such as ALS, Parkinson’s and Alzheimer’s disease,” Ye says. “The trouble with BDNF is one of delivery. It’s a protein, so it can’t cross the blood-brain barrier and degrades quickly.”

Working with Ye, postdoctoral fellow Sung-Wuk Jang identified a compound called 7,8-dihydroxyflavone that can duplicate BDNF’s effects on neurons and can protect them against damage in animal models of seizure, stroke and Parkinson’s disease. The compound’s selective effects suggest that it could be the founder of a new class of brain-protecting drugs. The results were published in Proceedings of the National Academy of Sciences.

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Posted on by Quinn Eastman in Neuro 1 Comment

Mapping mRNAs in the brain

If the brain acts like a computer, which of the brain’s physical features store the information? Flashes of electricity may keep memories and sensations alive for the moment, but what plays the role that hard drives and CDs do for computers?

A simple answer could be: genes turning on and off, and eventually, neurons growing and changing their shapes. But it gets more complicated pretty quickly. Genes can be regulated at several levels:

  • at the level of transcription — whether messenger RNA gets made from a stretch of DNA in the cell’s nucleus
  • at the level of translation — whether the messenger RNA is allowed to make a protein
  • at the level of RNA localization — where the mRNAs travel within the cell

Each neuron has only two copies of a given gene but will have many dendrites that can have more or less RNA in them. That means the last two modes of regulation offer neurons much more capacity for storing information.

Gary Bassell, a cell biologist at Emory, and his colleagues have been exploring how RNA regulation works in neurons. They have developed special tools for mapping RNA, and especially, microRNA — a form of RNA that regulates other RNAs.

In the dendrites of neurons, FMRP seems to control where RNAs end up

In the dendrites of neurons, FMRP seems to control where RNAs end up

Fragile X mental retardation protein (FMRP), linked to the most common inherited form of mental retardation, appears to orchestrate RNA traffic in neurons. Bassell and pharmacologist Yue Feng recently received a grant from the National Institute of Child Health and Development to study FMRP’s regulation of RNA in greater detail. The grant was one of several at Emory funded through the American Recovery and Reinvestment Act’s support for the NIH.

In the video interview above, Bassell explains his work on microRNAs in neurons. Below is a microscope image, provided by Bassell, showing the pattern of FMRP’s localization in neurons.

Posted on by Quinn Eastman in Neuro Leave a comment

Next steps in progesterone for brain injury

At a recent Society for Neuroscience (SFN) meeting, Emory researchers described their efforts to learn about optimizing progesterone for treatment of traumatic brain injury.

Researcher Donald Stein, PhD, Asa G. Candler Professor of Emergency Medicine at Emory School of Medicine, has shown that progesterone can protect damaged brain tissue. Stein is director of the Department of Emergency Medicine’s Brain Research Laboratory.

Donald G. Stein, PhD

Donald G. Stein, PhD

One of the Emory SFN presentations covered efforts to find progesterone analogues that are more water soluble. This work comes from Stein and his colleagues in collaboration with the laboratory of Dennis Liotta, PhD, Emory professor of chemistry.

Currently, the lack of water solubility limits delivery of progesterone, in that the hormone must be prepared hours ahead and cannot be kept at room temperature. Small chemical modifications may allow similar compounds with the same effects as progesterone to be given to patients closer to the time of injury.

According to the results, two compounds similar to progesterone showed an equivalent ability to reduce brain swelling in an animal model of traumatic brain injury.

The second Emory report described evidence that adding vitamin D to progesterone enhances the hormone’s effectiveness when applied to neurons under stress in the laboratory. Like progesterone, vitamin D is a steroid hormone that is inexpensive, has good safety properties and acts on many different biochemical pathways.

David Wright, MD

David Wright, MD

The authors showed that a low amount of vitamin D boosted the ability of progesterone to protect neurons from excito-toxicity , a principal cause of brain injury and cell death.

A new study at Emory, slated to begin early 2010, will evaluate progesterone’s effectiveness for treating traumatic brain injury in a multisite phase III clinical trial called ProTECT III.

The study follows earlier findings that showed giving progesterone to trauma victims shortly after brain injury appears to be safe and may reduce the risk of death and long-term disability.

David Wright, MD, assistant professor of emergency medicine at Emory School of Medicine is the national study’s lead investigator.

Michael Frankel, MD, Emory professor of neurology, will serve as site principal investigator of the clinical trial at Grady Memorial Hospital.

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