Before the cardiologist goes nuclear w/ stress #AHA17

Measuring troponin in CAD patients before embarking on stress testing may provide Read more

Virus hunting season open

Previously unknown viruses, identified by Winship + UCSF scientists, come from a patient with a melanoma that had metastasized to the Read more

#AHA17 highlight: cardiac pacemaker cells

Highlighting new research on engineering induced pacemaker cells from Hee Cheol Cho's Read more

stroke

Cell therapy clinical trial in stroke

Emory neurosurgeon Robert Gross was recently quoted in a Tennessee newspaper article about a clinical trial of cell therapy for stroke. He used cautionary language to set expectations.

“We’re still in the very early exploratory phases of this type of work,” Gross told the Chattanooga Times Free Press. “In these cases, a significant area of the brain has been damaged, and simply putting a deposit of undifferentiated cells into the brain and magically thinking they will rewire the brain as good as new is naive. None of us think that.”

A more preliminary study (just 18 patients) using the same approach at Stanford and University of Pittsburgh was published this summer in Stroke, which says it was the “first reported intracerebral stem cell transplant study for stroke in North America.” The San Diego Union Tribune made an effort to be balanced in how the results were described:

Stroke patients who received genetically modified stem cells significantly recovered their mobility… Outcomes varied, but more than a third experienced significant benefit.

The newspaper articles made us curious about what these cells actually are. They’re mesenchymal stromal cells, engineered with an extra modified Notch gene. That extra gene drives them to make more supportive factors for neurons, but it doesn’t turn them into neurons. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

NINDS director: neuroscience now largest ‘bucket of money’

On Friday, NINDS director Walter Koroshetz made an interesting remark in a lecture to Emory’s Department of Neurology. He said that in the 2016 National Institues of Health budget, neuroscience is now the largest “bucket of money,” especially with the recent boost in funding for Alzheimer’s research. That’s larger than the bucket for cancer. To be sure, biomedical research in general got a boost from Congress, with the NIH receiving its largest increase in a decade, and cancer is still a big deal!

Koroshetz explained that neuroscience research is spread out among NINDS (National Institute for Neurological Disorders and Stroke), NIMH (National Institute of Mental Health), NIDA (National Institute for Drug Abuse) and several others, while cancer research is concentrated at the National Cancer Institute. [Here’s some official category tracking that the NIH does – his breakdown checks out.]

Koroshetz highlighted a project from Dieter Jaeger and Garret Stanley that is part of the White House’s BRAIN Initiative focused on mapping brain circuits and connectivity. He also noted NINDS’s efforts in promoting translational research, since pharmaceutical companies were frustrated by repeated failures in the 1990s with difficult areas such as stroke, and the R35 mechanism for funding “outstanding investigators” for up to eight years continuously.

Posted on by Quinn Eastman in Neuro 2 Comments

Are TrkB agonists ready for translation into the clinic?

Our recent news item on Emory pathologist Keqiang Ye’s obesity-related research (Molecule from trees helps female mice only resist weight gain) understates how many disease models the proto-drug he and his colleagues have discovered, 7,8-dihydroxyflavone, can be beneficial in. We do mention that Ye’s partners in Australia and Shanghai are applying to begin phase I clinical trials with a close relative of 7,8-dihydroxyflavone in neurodegenerative diseases.

Ye’s 2010 PNAS paper covered models of Parkinson’s, stroke and seizure. Later publications take on animal models of depression, Alzheimer’s, fear learning, hearing loss and peripheral nerve injury. Although those findings begin to sound too good to be true, outside laboratories have been confirming the results (not 100 percent positive, but nothing’s perfect).  Plenty of drugs don’t make it from animal models into the clinic, but this is a solid body of work so far.

 

 

 

Posted on by Quinn Eastman in Neuro Leave a comment

Reviving drugs with anti-stroke potential, minus side effects

Neuroprotective drugs might seem impractical or improbable right now, after two big clinical trials testing progesterone in traumatic brain injury didn’t work out. But one close observer of drug discovery is predicting a “coming boom in brain medicines.” Maybe this research, which Emory scientists have been pursuing for a long time, will be part of it.

In the 1990s, neuroscientists identified a class of drugs that showed promise in the area of stroke. NMDA receptor antagonists could limit damage to the brain in animal models of stroke. But one problem complicated testing the drugs in a clinical setting: the side effects included disorientation and hallucinations.

Now researchers have found a potential path around this obstacle. The results were published in Neuron.

“We have found neuroprotective compounds that can limit damage to the brain during ischemia associated with stroke and other brain injuries, but have minimal side effects,” says senior author Stephen Traynelis, PhD, professor of pharmacology at Emory University School of Medicine.

“These compounds are most active when the pH is lowered by biochemical processes associated with injury of the surrounding tissue. This is a proof of concept study that shows this mechanism of action could potentially be exploited clinically in several conditions, such as stroke, traumatic brain injury and subarachnoid hemorrhage.” Read more

Posted on by Quinn Eastman in 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)
Posted on by Quinn Eastman in Uncategorized Leave a comment

A crystal ball for Lab Land: Top 5 topics in 2015

Alzheimer’s protein pathology

While a wise Dane once proposed that predictions are dangerous, especially concerning the future, it’s usually helpful to plan ahead. Here are five biomedical research topics we think will occupy our attention in 2015.

1. Alzheimer’s We’re hearing discordant music coming from Alzheimer’s researchers. Large pharmaceutical companies are shutting down clinical trials in frustration, but researchers keep coming forward with biomarkers that might predict future disease. This confusing situation calls for some new thinking. Allan Levey, Jim Lah and colleagues have been preparing the way for a “beyond the usual suspects” look at Alzheimer’s disease. We are looking forward to Levey’s appearance at the 2015 AAAS meeting and to drug discovery wizard Keqiang Ye’s continuing work on new therapeutic targets.

2. Ebola While the scare over Ebola in the United States may be over (we hope so!), the outbreak continues to devastate countries in West Africa. Clinical trials testing vaccines and experimental drugs are underway or will be soon. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Clot dissolver tPA’s tardy twin could aid in stroke recovery

Emory researchers led by neurologist Manuel Yepes, MD have identified a protein released by neurons while the brain is recovering from a stroke. The results were published online today in Journal of Neuroscience.

The protein, called urokinase-type plasminogen activator or uPA, has been approved by the FDA to dissolve blood clots in the lungs. It has been tested in clinical trials in some countries as a treatment for acute stroke.

The Emory team’s findings suggest that in stroke, uPA’s benefits may extend beyond the time when doctors’ principal goal is dissolving the blood clot that is depriving the brain of blood.
Instead, uPA appears to help brain cells recover from the injuries induced by loss of blood flow. Treating mice with uPA after an experimental stroke can improve their recovery of motor function, the researchers found.

Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Evaluating a different way to measure LDL

What is the most important measurement of cholesterol or lipids in the blood, when it comes to cardiovascular disease risk? LDL-C [low density lipoprotein cholesterol], is often called “bad cholesterol” because it is linked to atherosclerosis, but the landscape is always shifting. Even as cardiologists across the country get used to the new AHA/ACC guidelines, which call for changes in how physicians and patients view LDL-C, new research is focusing attention on other related markers. For example, a recent pair of studies in the New England Journal of Medicine identify gene mutations that lower both triglycerides and heart disease risk, suggesting that drugs that target that gene pathway could be beneficial. A new paper in Atherosclerosis, coauthored by Emory’s Terry Jacobson, looks at LDL-P, a different way of looking at LDL that has been proposed to be a better measure of cardiovascular disease risk. Jacobson is director of the Office of Health Promotion and Disease Prevention at Grady Health Systems. Read more

Posted on by Quinn Eastman in Heart Leave a comment

Progesterone could become tool vs glioblastoma

The hormone progesterone could become part of therapy against the most aggressive form of brain cancer. High concentrations of progesterone kill glioblastoma cells and inhibit tumor growth when the tumors are implanted in mice, researchers have found.

The results were recently published in the Journal of Steroid Biochemistry and Molecular Biology.

Glioblastoma is the most common and the most aggressive form of brain cancer in adults, with average survival after diagnosis of around 15 months. Surgery, radiation and chemotherapy do prolong survival by several months, but targeted therapies, which have been effective with other forms of cancer, have not lengthened survival in patients fighting glioblastoma.

The lead author of the current paper is assistant professor of emergency medicine Fahim Atif, PhD. The findings with glioblastoma came out of Emory researchers’ work on progesterone as therapy for traumatic brain injury and more recently, stroke. Atif, Donald Stein and their colleagues have been studying progesterone for the treatment of traumatic brain injury for more than two decades, prompted by Stein’s initial observation that females recover from brain injury more readily than males. There is a similar tilt in glioblastoma as well: primary glioblastoma develops three times more frequently in males compared to females.

These results could pave the way for the use of progesterone against glioblastoma in a human clinical trial, perhaps in combination with standard-of-care therapeutic agents such as temozolomide. However, Stein says that more experiments are necessary with grafts of human tumor cells into animal brains first. His team identified a factor that may be important for clinical trial design: progesterone was not toxic to all glioblastoma cell lines, and its toxicity may depend on whether the tumor suppressor gene p53 is mutated.

Atif, Stein, and colleague Seema Yousuf found that low, physiological doses of progesterone stimulate the growth of glioblastoma tumor cells, but higher doses kill the tumor cells while remaining nontoxic for healthy cells. Similar effects have been seen with the progesterone antagonist RU486, but the authors cite evidence that progesterone is less toxic to healthy cells. Progesterone has also been found to inhibit growth of neuroblastoma cells (neuroblastoma is the most common cancer in infants), as well as breast, ovarian and colon cancers in cell culture and animal models.

 

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

Blood biomarkers may help predict risk in stroke and TBI


Biomarkers circulating in the bloodstream may serve as a predictive window for recurrent stroke risk and also help doctors accurately assess what is happening in the brains of patients with acute traumatic brain injury (TBI).

Michael Frankel, MD

Researchers at Emory University School of Medicine, led by principal investigator Michael Frankel, MD, Emory professor of neurology and director of Grady Memorial Hospital’s Marcus Stroke & Neuroscience Center, are studying biomarkers as part of two ancillary studies of blood samples using two grants from the National Institutes of Health.

In the $1.47 million, four-year grant called “Biomarkers of Ischemic Outcomes in Intracranial Stenosis” (BIOSIS), Emory researchers are analyzing blood samples from 451 patients from around the country who were enrolled in a study known as SAMMPRIS (Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis), the first randomized, multicenter clinical trial designed to test whether stenting intracranial arteries would prevent recurrent stroke.

Researchers in the SAMMPRIS study recently published their results in the New England Journal of Medicine, showing that medical management was more effective than stenting in preventing recurrent strokes in these patients. Frankel’s BIOSIS research team is using blood samples from these same patients to continue learning more about the molecular biology of stroke to predict risk of a stroke occurring in the future.

“Our goal is to learn more about stroke by studying proteins and cells in the blood that reflect the severity of disease in arteries that leads to stroke. If we can test blood samples for proteins and cells that put patients at high risk for stroke, we can better tailor treatment for those patients,” says Frankel.

Patients with narrowed brain arteries, known as intracranial stenosis, have a particularly high risk of disease leading to stroke. At least one in four of the 795,000 Americans who have a stroke each year will have another stroke within their lifetime. Within five years of a first stroke, the risk for another stroke can increase more than 40 percent. Recurrent strokes often have a higher rate of death and disability because parts of the brain already injured by the original stroke may not be as resilient.

The other study, “Biomarkers of Injury and Outcome in ProTECT III” (BIO-ProTECT)” is a $2.6 million, five-year NIH grant in which Frankel’s team will use blood to determine what is happening in the brain of patients with acute TBI.  The blood samples are from patients enrolled in the multicenter clinical trial ProTECT III (Progesterone for Traumatic brain injury, Experimental Clinical Treatment), led by Emory Emergency Medicine Professor, David Wright, MD, to assesses the use of progesterone to treat TBI in 1,140 patients at 17 centers nationwide.

In the BIO-ProTECT study, Emory is collaborating with the Medical University of South Carolina, the University of Pittsburgh, the University of Michigan and Banyan Biomarkers.

TBI is the leading cause of death and disability among young adults in the US and worldwide. According to the Centers for Disease Control and Prevention, approximately 1.4 million Americans sustain a traumatic brain injury each year, leading to 275,000 hospitalizations, 80,000 disabilities, and 52,000 deaths.

Acute TBI leads to a cascade of cellular events set in motion by the initial injury that ultimately lead to cerebral edema (swelling of the brain), cellular disruption and sometimes death. Tissue breakdown leads to the release of proteins into the bloodstream. These proteins may serve as useful biomarkers of the severity of the injury and perhaps provide useful information about response to treatment.

Using the large patient group in the ProTECT III trial, the researchers hope to validate promising TBI biomarkers as predictors of clinical outcome and also evaluate the relationship between progesterone treatment, biomarker levels and outcome.

“If we can better determine the amount of brain injury with blood samples, we can use blood to help doctors better assess prognosis for recovery, and, hopefully whether a patient will respond to treatment with progesterone,” says Frankel.

Posted on by Juliette Merchant in Neuro Leave a comment