The blue spot: where seeds of destruction begin

Learn more about the locus coeruleus, a "canary in the coal Read more

Complexity of NMDA receptor drug discovery target revealed

GluN2C heterotrimer dominant in cerebellum + thalamus -- possibly important target for Read more

Measuring sleepiness: alternatives to five naps

If the MSLT is unsatisfactory, what should replace or supplement Read more

Parkinson’s Disease

Lab Land looking back: Top ten themes for 2014

It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After diverting some of these topics into the 2015 crystal ball, I corralled them into themes.
1. Cardiac cell therapy
PreSERVE AMI clinical trial led by cardiologist Arshed Quyyumi. Emory investigators developing a variety of approaches to cardiac cell therapy.
2. Mobilizing the body’s own regenerative potential
Ahsan Husain’s work on how young hearts grow. Shan Ping Yu’s lab using parathyroid hormone bone drug to mobilize cells for stroke treatment.
3. Epigenetics
Many colors in the epigenetic palette (hydroxymethylation). Valproate – epigenetic solvent (anti-seizure –> anti-cancer). Methylation in atherosclerosis model (Hanjoong Jo). How to write conservatively about epigenetics and epigenomics.
4. Parkinson’s disease therapeutic strategies
Container Store (Gary Miller, better packaging for dopamine could avoid stress to neurons).
Anti-inflammatory (Malu Tansey, anti-TNF decoy can pass blood-brain barrier).
5. Personal genomics/exome sequencing
Rare disease diagnosis featured in the New Yorker. Threepart series on patient with GRIN2A mutation.
6. Neurosurgeons, like Emory’s Robert Gross and Costas Hadjpanayis, do amazing things
7. Fun vs no fun
Fun = writing about Omar from The Wire in the context of drug discovery.
No fun (but deeply moving) = talking with patients fighting glioblastoma.
8. The hypersomnia field is waking up
Our Web expert tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
Image guided cancer surgery (Shuming Nie/David Kooby). Cancer immunotherapy chimera (Jacques Galipeau). Fine tuning old school chemo drug cisplatin (Paul Doetsch)
10. Tie between fructose effects on adolescent brain (Constance Harrell/Gretchen Neigh) and flu immunology (embrace the unfamiliar! Ali Ellebedy/Rafi Ahmed)
Posted on by Quinn Eastman in Uncategorized Leave a comment

Explainer: the locus coeruleus

The locus coeruleus is a part of the brain that has been getting a lot of attention recently from Emory neuroscience researchers.

The locus coeruleus is the biggest source of the neurotransmitter norepinephrine in the brain. Located deep in the brainstem, it has connections all over the brain, and is thought to be involved in arousal and attention, stress, memory, the sleep-wake cycle and balance.

Researchers interested in neurodegenerative disease want to look at the locus coeruleus because it may be one of the first structures to degenerate in diseases such as Alzheimer’s and Parkinson’s. In particular, the influential studies of German neuro-anatomist Heiko Braak highlight the locus coeruleus as a key “canary in the coal mine” indicator of neurodegeneration.

That’s why neurologist Dan Huddleston, working with biomedical imaging specialists Xiangchuan Chen and Xiaoping Hu and colleagues at Emory, has been developing a method for estimating the volume of the locus coeruleus by magnetic resonance imaging (MRI). Their procedure uses MRI tuned in such a way to detect the pigment neuromelanin (see panel), which accumulate in both the locus coeruleus and in the substantia nigra. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Anti-inflammatory drug prevents neuron loss in Parkinson’s model

A lot of evidence has piled up suggesting that inflammation plays a big role in the progression of Parkinson’s.

Immune system genes are linked to disease risk. People who regularly take NSAIDs such as ibuprofen have lower risk. Microglia, the immune system’s ambassadors to the brain, have been observed in PD patients.

Malu Tansey and her postdoc CJ Barnum make a convincing case for an anti-inflammatory — specifically, anti-TNF– therapy to Parkinson’s. They’ve been working with the Michael J. Fox Foundation for Parkinson’s Research to push this promising approach forward. Please check it out.

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

Parkinson’s drug discovery: visit the dopamine container store

In a recent PNAS paper, Gary Miller and colleagues at Rollins School of Public Health outline a potential therapeutic approach to Parkinson’s disease that I’m going to call the Container Store approach.

If you have a mess in your kitchen or basement workshop, you might need more or better containers to hold your tools. Analogously, problems in Parkinson’s disease can be traced back to a lack of effective containers for the brain communication chemical dopamine.

Read more

Posted on by Quinn Eastman in Neuro Leave a comment

A Sherer of Parkinson’s research

The name of the guest speaker at Emory’s Office of Technology Transfer’s annual celebration on March 7 provoked some double takes around campus last week.

Todd B. Sherer, PhD

Todd B. Sherer, PhD

Todd B. Sherer, PhD, CEO of the Michael J. Fox Foundation for Parkinson’s Research (MJFF), described how the Fox Foundation is trying to build bridges between the worlds of basic and clinical research to speed development of new drugs for the treatment of Parkinson’s disease, and offered a ray ban outlet perspective on how independent research funders can help move drug candidates from the lab to the clinic and closer to market.

Sherer, a former postdoctoral fellow at Emory, also has the same first and last name (but not middle initial!) as OTT’s director. Sherer – the one who works for the Fox Foundation – joined that non-profit charity’s staff in 2004. While at Emory, he worked on models for Parkinson’s based on exposure to the pesticide rotenone, alongside Ranjita Betarbet, Gary Miller and J. Timothy Greenamyre, who himself moved on to the University of Pittsburgh in 2005.

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Posted on by Quinn Eastman in Neuro Leave a comment

Neuroinflammation: a different way to look at Parkinson’s disease

Emory physiologist Malu Tansey and her colleagues are using recent insights into the role of inflammation in Parkinson’s disease to envision new treatments. One possible form this treatment strategy could take would be surprisingly simple, and comparable to medications that are approved for rheumatoid arthritis.

Malu Tansey, PhD

Understanding the role of inflammation in Parkinson’s requires a shift in focus. Many Parkinson’s researchers understandably emphasize the neurons that make the neurotransmitter dopamine. They’re the cells that are dying or already lost as the disease progresses, leading to tremors, motor difficulties and a variety of other symptoms.

But thinking about the role of inflammation in Parkinson’s means getting familiar with microglia, the immune system’s field reps within the brain. At first, it was thought that the profusion of microglia in the brains of Parkinson’s patients was just a side effect of neurodegeneration. The neurons die, and the microglia come in to try to clean up the debris.

Now it seems like microglia and inflammation might be one of the main events, if not the initiating event.

“Something about the neurons’ metabolic state, whether it’s toxins, oxidative stress, unfolded proteins, or a combination, makes them more sensitive. But inflammation, sustained by the presence of microglia, is what sends them over the edge,” Tansey says.

She says that several recent studies have led to renewed attention to this area:

  1. In vivo PET imaging using a probe for microglia has allowed scientists to see inflammation starting early in the progression of Parkinson’s (see figure below)
  2. Epidemiology studies show that taking ibuprofen regularly is linked to lower incidence of Parkinson’s
  3. Experiments with animal models of genetic susceptibility demonstrate that inflammatory agents like endotoxin can accelerate neurodegeneration
  4. Genomics screens have identified HLA-DR, an immune system gene, as a susceptibility marker for Parkinson’s (Emory’s Stewart Factor was a co-author on this paper)

Popping a few ibuprofen pills everyday for prevention and possibly damaging the stomach along the way is probably not going to work well, Tansey says. It should be possible to identify a more selective way to inhibit microglia, which may be able to inhibit disease progression after it has started.

Activated microglia in the midbrain and striatum of a Parkinson's patient

Targeting TNF (tumor necrosis factor), an important inflammatory signaling molecule, may be one way to go. Anti-TNF agents are already used to treat rheumatoid arthritis and inflammatory bowel disease. This January, Tansey and her co-workers published a paper showing that a gene therapy approach using decoy TNF can reduce neuronal loss in a rat model of Parkinson’s. More recently, her lab has also shown that targeting the gene RGS10 is another way to inhibit microglia and reduce neurodegeneration in the same models.

It is important to note that in the rat studies, they do surgery and put the gene therapy viral vector straight into the brain. She says it might possible to perform peripheral gene therapy with the microglia, or even anti-TNF medical therapy. In terms of mechanism, decoy (technically, dominant negative) TNF is more selective and may avoid the side effects, such as opportunistic infections, of existing anti-TNF agents.

Posted on by Quinn Eastman in Neuro 1 Comment

Shedding light on the vitamin D-Parkinson’s connection

Vitamin D may be called a vitamin, but it’s not. That’s because we can make it by exposing our skin to sunshine. So, technically that makes vitamin D a hormone–a steroid hormone to be exact. In fact, we get most of our exposure to vitamin D directly from sunshine and some from foods such as milk, fortified orange juice and oily fishes like salmon.

But no matter what you call it or where you get it, vitamin D is vital to growth, development and maintenance of our cells. Doctors have known for decades that vitamin D promotes calcium uptake and bone formation, but evidence is accumulating that it regulates the immune system and the development of the nervous system. Growing evidence suggests a link between low vitamin D levels and Parkinson’s disease, but whether this is a cause-and-effect relationship is unknown.

Marian Evatt, MD

That’s why Emory neurologist Marian Evatt, MD, and her colleagues are conducting a clinical trial exploring the effects of vitamin D supplementation on patients with Parkinson’s disease who have low vitamin D levels. The study also includes further epidemiological studies of vitamin D in Parkinson’s disease.

Parkinson’s disease affects nerve cells in several parts of the brain, particularly those that use the chemical messenger dopamine to control movement. The most common symptoms of Parkinson’s disease are tremor, stiffness and slowness of movement.

“Vitamin D has become associated with many chronic diseases: diabetes, hypertension, cardiovascular disease, and some of the autoimmune diseases, including multiple sclerosis,” says Evatt. “But we haven’t yet determined the specific effect of vitamin D in specific conditions because it has such broad effects.”

To hear Evatt talk about what vitamin D is, what it does, and why we need it, please go to Emory’s latest Sound Science podcast.

Posted on by Robin Tricoles 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.

Read more

Posted on by Quinn Eastman in Neuro 1 Comment

Michael J. Fox Foundation supports Emory research

The Michael J. Fox Foundation for Parkinson’s Research just announced plans to fund Emory pharmacology researcher Zixu Mao in his work to validate therapeutic targets for Parkinson’s disease (PD).

Zixu Mao, PhD

Zixu Mao, PhD

The two-year, $250,000 grant will fund research in Mao’s lab in the departments of neurology and pharmacology. He and his team hope to verify whether a particular protein – MEF2D – may be a good drug target in models of PD. If it is, his efforts will provide the basis for further research to identify ways to manipulate the activity of this protein as a way to treat PD.

Mao says this type of study is very important Maglie Calcio to allow the transition from findings made by basic research to more clinically relevant discoveries and is generally difficult to get funded by other major funding sources.

The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson’s disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson’s today. Learn more about Mao’s research.

Posted on by Jennifer Johnson in Uncategorized Leave a comment