Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more
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placebo effect

Skin disease studies go deep: depression/inflammation insight

The placebo effect plays a big role in clinical trials for mood disorders such as depression. Emory psychiatrist Andy Miller hit upon something several years ago that could clear a path around the placebo effect.

Miller and his colleagues have been looking at the connection between inflammation and depression, whose evolutionary dimensions we have previously explored. They’ve examined the ability of inflammation-inducing treatments for hepatitis C and cancer to trigger symptoms of depression, and have shown that the anti-inflammatory drug infliximab (mainly used for rheumatoid arthritis) can resolve some cases of treatment-resistant depression. [Lots of praise for Miller in this September 2017 Nature Medicine feature.]

A recent paper in Psychotherapy and Psychosomatics from Miller and psychiatry chair Mark Rapaport looks at clinical trials testing an anti-inflammatory drug against psoriasis, to see whether participants’ depressive symptoms improved. This sidesteps a situation where doctors’ main targets are the patients’ moods.

When it comes to approving new antidepressants, the FDA is still probably going to want a frontal assault on depression, despite provisions in the 21st Century Cures Act to broaden the types of admissible evidence.

“These studies emphasize how difficult it is to interpret findings when these drugs are treating more than one problem,” Miller says. “Better to have a simpler study with just depression.”

Still, this line of research could clarify who could benefit from anti-inflammatory treatments and illuminate viable biomarkers and pathways. Two studies now underway at Emory specifically recruit patients with high levels of the inflammatory marker CRP, which Miller’s previous study showed was helpful in predicting response to infliximab.

The new paper results from a collaboration with Eli Lilly. Lilly’s ixekizumab (commercial name: Taltz) is an antibody against the cytokine IL-17A, used to treat moderate to severe psoriasis. Taltz was approved by the FDA in 2016, after clinical trials published in the New England Journal of Medicine. Read more

Posted on October 20, 2017 by Quinn Eastman in Immunology, Neuro Leave a comment

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 August 30, 2016 by Quinn Eastman in Neuro Leave a comment

Sidestepping the placebo effect when studying depression

Research on depression must deal with a major obstacle: the placebo effect. This is the observation that patients improve in response to the sugar pills given as controls in clinical studies.

Clinical trial designers can incorporate various clever strategies to minimize the placebo effect, which is actually comprised of several statistical and psychological factors. Investigators can try to enhance, dissect or even “harness” them. [A recent piece in the New York Times from Jo Marchant focuses on the placebo effect in studies of pain relief.]

Emory psychiatrist Andrew Miller and his team have been developing a different approach over the last few years: studying symptoms of depression in people who are being treated for something else. This allows them to sidestep, at least partially, the cultural construct of depression, from William Styron to Peter Kramer to direct-to-consumer television ads.

Interferon alpha, a treatment used against hepatitis C virus infection and some forms of cancer, is a protein produced by the immune system that spurs inflammation. It also can induce symptoms of depression, such as fatigue and malaise. There are some slight differences with psychiatric depression, which Miller’s team describes here (less guilt!), but they conclude that there is a “high degree of overlap.”

Miller and his colleagues, including Jennifer Felger and Ebrahim Haroon, have documented how interferon-alpha-induced inflammation affects the brains of hepatitis C and cancer patients in several papers. That research, in turn, informs their more recent fruitful investigations of inflammation in the context of major depression. More on that soon.

Posted on January 13, 2016 by Quinn Eastman in Immunology, Neuro Leave a comment