Head to head narcolepsy/hypersomnia study

At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy. The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 Read more

Anti-inflammatory approach suppresses cancer metastasis in animal models

An anti-inflammatory drug called ketorolac, given before surgery, can promote long-term survival in animal models of cancer metastasis, a team of scientists has found. The research suggests that flanking chemotherapy with ketorolac or similar drugs -- an approach that is distinct from previous anti-inflammatory cancer prevention efforts -- can unleash anti-tumor immunity. The findings, published in Journal of Clinical Investigation, also provide a mechanistic explanation for the anti-metastatic effects of ketorolac, previously observed in human Read more

I3 Venture awards info

Emory is full of fledgling biomedical proto-companies. Some of them are actual corporations with employees, while others are ideas that need a push to get them to that point. Along with the companies highlighted by the Emory Biotech Consulting Club, Dean Sukhatme’s recent announcement of five I3 Venture research awards gives more examples of early stage research projects with commercial potential. This is the third round of the I3 awards; the first two were Wow! Read more

proteomics

Beyond the amyloid hypothesis: proteins that indicate cognitive stability

If you’re wondering where Alzheimer’s research might be headed after the latest large-scale failure of a clinical trial based on the “amyloid hypothesis,” check this out.

Plaques. Tangles. Clumps. These are all pathological signs of neurodegenerative diseases that scientists can see under the microscope. But they don’t explain most of the broader trends of cognitive resilience or decline in aging individuals. What’s missing?

A recent proteomics analysis in Nature Communications from Emory researchers identifies key proteins connected with cognitive trajectory – meaning the rate at which someone starts to decline and develop mild cognitive impairment or dementia.

This paper fits in with the multi-year push for “unbiased” Alzheimer’s/aging research at Emory. The lead and senior authors are Aliza and Thomas Wingo, with proteomics from biochemist Nick Seyfried and company.

The proteins the Emory team spotlights are not the usual suspects that scientists have been grinding on for years in the Alzheimer’s field, such as beta-amyloid and tau. They’re proteins connected with cellular energy factories (mitochondria) or with synapses, the connections between brain cells.

“Our most notable finding is that proteins involving mitochondrial activities or synaptic functions had increased abundance among individuals with cognitive stability regardless of the burden of β-amyloid plaques or neurofibrillary tangles,” the authors write. “Taken together, our findings and others highlight that mitochondrial activities would be a fruitful research target for early prevention of cognitive decline and enhancement of cognitive stability.” Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Emory neuro-researchers in Alzforum

Just a shoutout regarding Emory folks in Alzforum, the research news site focusing on Alzheimer’s and other neurodegenerative disorders.

Alzforum recently highlighted proteomics wizard Nick Seyfried’s presentation at a June meeting in Germany (Alzheimer’s Proteomics Treasure Trove). This includes work from the Emory ADRC and Baltimore Longitudinal Study of Aging that was published in Cell Systems in December: the first large-scale systems biology analysis of post-mortem brain proteins in Alzheimer’s. The idea is to have a fresh “unbiased” look at proteins involved in Alzheimer’s.

Also, neuroscientists Malu Tansey and Tom Kukar have been teaming up to provide detailed comments on papers being reported in Alzforum. Here’s one on inflammation related to gene alterations in frontotemporal dementia, and another on auto-immune responses in Parkinson’s.

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Proteomics making fantastic routine

Much of basic biomedical research concerns proteins. The enzymes that keep cells running, the regulators and receptors that control what our cells do, the antibodies that defend us against invaders — all of these are proteins.

That means every day, scientists are asking questions like:

What’s happening to my favorite protein? Is there more or less of it in this sample? What other proteins work with it or stick to it?

That’s where a proteomics core facility comes in. Given a mixture of hundreds or even thousands of proteins, proteomics specialists can separate, identify and quantify them.Proteomics1smaller

Researchers in the areas of Alzheimer’s disease, cancer metabolism, schizophrenia and vaccines all make use of Emory’s proteomics core facility. It was key to the Alzheimer’s Disease Research Center’s 2013 discovery of a new form of Alzheimer’s disease protein pathology.

Director Nick Seyfried reports that the core has acquired close to $3 million in sophisticated mass spectrometry equipment in the last few years. The Emory Integrated Proteomics Core, one of the Emory Integrated Core Facilities, is supported in part by the Winship Cancer Institute, the Atlanta Clinical and Translational Science Institute, and a recently renewed grant for ENNCF (Emory Neurosciences NINDS Core Facilities).

Protein mass spectrometry is like Wonkavision

There’s a scene in both the 1971 and 2005 film adaptations of Roald Dahl’s Charlie and the Chocolate Factory, in which a chocolate bar is separated into millions of tiny pieces and sent flying across a clean room. Protein mass spectrometry resembles the first part of this process. Read more

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Beyond the usual suspects among Alzheimer’s proteins

If you’ve been paying attention to Alzheimer’s disease research, you’ve probably read a lot about beta-amyloid. It’s a toxic protein fragment that dominates the plaques that appear in the brains of people with Alzheimer’s. Many experimental therapies for Alzheimer’s target beta-amyloid, but so far, they’ve not proven effective.

That could be for several reasons. Maybe those treatments started too late to make a difference. But an increasing number of Alzheimer’s researchers are starting to reconsider the field’s emphasis on amyloid. Nature News has a feature this week explaining how the spotlight is shifting to the protein ApoE, encoded by the gene whose variation is responsible for the top genetic risk factor for Alzheimer’s.

In line with this trend, Emory’s Alzheimer’s Disease Research Center recently received a five-year, $7.2 million grant to go beyond the usual suspects like beta-amyloid. Emory will lead several universities in a project to comprehensively examine proteins altered in Alzheimer’s. You’ve heard of the Cancer Genome Atlas? Think of this as the Alzheimer’s Proteome Atlas, potentially addressing the same kind of questions about which changes are the drivers and which are the passengers.

Emory’s back-to-basics proteomics approach has already yielded some scientific fruit, uncovering changes in proteins involved in RNA splicing and processing. Also, the Nature feature also has some background on a clinical trial called TOMMORROW, which Emory’s ADRC is participating in.

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