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

Parkinson’s Disease

More pieces in Parkinson’s puzzle: VMAT2 and SV2C

The drug target VMAT2 has appeared in biomedical news lately because of a pair of FDA approvals. One medicine treats the iatrogenic movement disorder tardive dyskinesia, the first approved to do so, and the other is for symptoms of Huntington’s disease.

Gary Miller, PhD

When Emory folks see VMAT2, they should think of two things: the neurotransmitter dopamine, and Parkinson’s research conducted by Gary Miller and his colleagues. They have made a case that activators of VMAT2 would be beneficial in Parkinson’s, but the drugs in the news were inhibitors, and presumably would make Parkinson’s worse.

VMAT2 (vesicular monoamine transporter 2) is responsible for transporting dopamine into synaptic vesicles, tiny packages for delivery. As Miller’s lab has shown, mice deficient in VMAT2 can be a model for the non-motor and motor aspects of Parkinson’s. In these mice, not only are certain nervous system functions impaired, but the dopamine packaging problem inflicts damage on the neurons.

Miller’s more recent work on a related molecule called SV2C is puzzling, but intriguing. The gene encoding SV2C had attracted attention because of its connection to the striking ability of cigarette smoking to reduce Parkinson’s risk, possibly mediated by nicotine’s effect on dopamine in the brain.

I say puzzling because SV2C’s role in brain cells can’t be described as easily as VMAT2’s. Read more

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Parkinson’s disease: hold the AMPs

Pathologist Keqiang Ye and colleagues recently published a paper in PNAS that may have implications for Parkinson’s disease pathology and treatment strategies.

The protein alpha-synuclein is a bad actor in PD (nice explainer from Michael J. Fox Foundation); it’s a major constituent of Lewy bodies, the protein clumps that appear in PD patients’ brains, and there is a genetic link too. Alpha-synuclein seems to bring other proteins into the clumps, which may disrupt neuron function.

In particular, it sequesters PIKE-L, an inhibitor of AMP kinase, leading to AMP kinase hyperactivation and cell death. AMP kinase is a metabolic regulator activated by metformin, a common treatment for diabetes. So activating AMP kinase in some situations can be good for your body; however for the neurons affected by alpha-synuclein, activating it too much is bad.

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Breath test for Parkinson’s?

Using one to see into the other. Left: canister for breath sample. Right: basal ganglia, a region of the brain usually affected by Parkinson’s.

Scientists think that it may be possible to detect signs of Parkinson’s disease through a breath test.

The Michael J. Fox Foundation for Parkinson’s Research is supporting a clinical study at Emory that will probe this idea. Neuro-immunologist Malu Tansey is working with Hygieia, a Georgia-based company that has developed technology for analyzing volatile organic compounds present in exhaled air.

From the MJFF’s blog:

By collecting and analyzing breath samples in 100 people (50 non-smoking early-stage PD patients and 50 age and sex-matched controls), the researchers hope to define a unique inflammatory PD-specific breath fingerprint that could be used to predict and monitor disease in combination with blood analyses of conventional or newly discovered biomarkers.

“We hypothesize that breath volatile organic compounds (BVOCs) fingerprinting can enable sensitive and specific measures of ongoing inflammation and other processes implicated in the development and/or progression of PD, and thus could represent an early detection tool,” Tansey says.

If results indicate moving forward, Tansey says it will be important to compare the breath sample method against blood tests for inflammatory markers. Other reports on the breath test approach for Parkinson’s have been encouraging. Read more

Posted on by Quinn Eastman in Neuro 1 Comment

Emory labs on LabTV

This summer, video producers from the web site LabTV came to two laboratories at Emory. We are pleased to highlight the first crop of documentary-style videos.

LabTV features hundreds of young researchers from universities and institutes around the United States, who tell the public about themselves and their research. The videos include childhood photos and explanations from the scientists about what they do and what motivates them. Screen Shot 2015-12-18 at 9.14.51 AM

The two Emory labs are: Malu Tansey’s lab in the Department of Physiology, which studies the intersection of neuroscience and immunology, focusing on neurodegenerative disease, and Mike Davis’ lab in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, which is developing regenerative approaches and technologies for heart disease in adults and children. Read more

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Risk triangle: immune gene, insecticide, Parkinson’s

Genetic variation and exposure to pesticides both appear to affect risk for Parkinson’s disease. A new study has found a connection between these two risk factors, in a way that highlights a role for immune responses in progression of the disease.

The results are published in the inaugural issue of NPJ Parkinson’s Disease.

The findings implicate a type of pesticide called pyrethroids, which are found in the majority of commercial household insecticides, and are being used more in agriculture as other insecticides are being phased out. Although pyrethroids are neurotoxic for insects, exposure to them is generally considered safe for humans by federal authorities.

The study is the first making the connection between pyrethroid exposure and genetic risk for Parkinson’s, and thus needs follow-up investigation, says co-senior author Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine.

The genetic variation the team probed, which has been previously tied to Parkinson’s in larger genome-wide association studies, was in a non-coding region of a MHC II (major histocompatibility complex class II) gene, part of a group of genes that regulate the immune system.

“We did not expect to find a specific association with pyrethroids,” Tansey says. “It was known that acute exposure to pyrethroids could lead to immune dysfunction, and that the molecules they act on can be found in immune cells; now we need to know more about how longer-term exposure affects the immune system in a way that increases risk for Parkinson’s.”

“There is already ample evidence that brain inflammation or an overactive immune system can drive the progression of Parkinson’s. What we think may be happening here is that environmental exposures may be altering some people’s immune responses, in a way that promotes chronic inflammation in the brain.”

For this study, Emory investigators led by Tansey and Jeremy Boss, PhD, chair of microbiology and immunology, teamed up with Stewart Factor, DO, head of Emory’s Comprehensive Parkinson’s Disease Center, and public health researchers from UCLA led by Beate Ritz, MD, PhD. The first author of the paper is MD/PhD student George T. Kannarkat.

The UCLA researchers used a California state geographical database covering 30 years of pesticide use in agriculture. They defined exposure based on proximity (someone’s work and home addresses), but did not measure levels of pesticides in the body. Pyrethroids are thought to decay relatively quickly, especially in sunlight, with half-lives in soil of days to weeks. Read more

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

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)
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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

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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.

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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

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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.

Read more

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