Study finds ‘important implications’ to understanding immunity against COVID-19

New research from Emory University indicates that nearly all people hospitalized with COVID-19 develop virus-neutralizing antibodies within six days of testing positive. The findings will be key in helping researchers understand protective immunity against SARS-CoV-2 and in informing vaccine development. The test that Emory researchers developed also could help determine whether convalescent plasma from COVID-19 survivors can provide immunity to others, and which donors' plasma should be used. The antibody test developed by Emory and validated Read more

Emory plays leading role in landmark HIV prevention study of injectable long-acting cabotegravir

Emory University played a key role in a landmark international study evaluating the safety and efficacy of the long-acting, injectable drug, cabotegravir (CAB LA), for HIV prevention. The randomized, controlled, double-blind study found that cabotegravir was 69% more effective (95% CI 41%-84%) in preventing HIV acquisition in men who have sex with men (MSM) and transgender women who have sex with men when compared to the current standard of care, daily oral emtricitabine/tenofovir disoproxil fumarate Read more

Yerkes researchers find Zika infection soon after birth leads to long-term brain problems

Researchers from the Yerkes National Primate Research Center have shown Zika virus infection soon after birth leads to long-term brain and behavior problems, including persistent socioemotional, cognitive and motor deficits, as well as abnormalities in brain structure and function. This study is one of the first to shed light on potential long-term effects of Zika infection after birth. “Researchers have shown the devastating damage Zika virus causes to a fetus, but we had questions about Read more

clinical trials

Update on pancreatic cancer: images and clinical trial

In 2018, Winship magazine had a feature story on pancreatic cancer. Our team developed an illustration that we hoped could convey the tumors’ complex structure, which contributes to making them difficult to treat. Oncologist Bassel El-Rayes described how the tumors recruit other cells to form a protective shell.

“If you look at a tumor from the pancreas, you will see small nests of cells embedded in scar tissue,” he says. “The cancer uses this scar tissue as a shield, to its own advantage.”

With El-Rayes and fellow oncologist Walid Shaib, Greg Lesinski’s lab recently published a paper in JCI Insight. The point of the paper was to look at how chemotherapy changes immune activity in the tumor microenvironment, but we also get vivid images giving us a glimpse of those nests. It helps to view these images as large as possible, so please check them out at the journal’s site, which has no paywall.

Regions stained green are tumor-rich; red regions are immune cell-rich, and blue regions are rich in stromal cells (stellate/fibroblast cells). The goal is to get immune cells to envelop the tumors more, like in square 8.

The 2018 magazine story also laid out some of Lesinski’s and El-Rayes’ ideas.

Based on his lab’s recent success in animal models, Lesinski thinks that combining an immunotherapy drug with agents that stop IL-6 could pry open pancreatic cancers’ protective shells. In those experiments, the combination resulted in fewer stellate cells and more T cells in the tumors. Fortunately, a couple of “off-the-shelf” options, drugs approved for rheumatoid arthritis, already exist for targeting IL-6, Lesinski says.

On that theme, we noticed that a clinical trial was posted on clinicaltrials.gov in December that implements those proposals: “Siltuximab and Spartalizumab in Patients With Metastatic Pancreatic Cancer”. El-Rayes is the principal investigator, and it is not yet recruiting. Siltuximab is an antibody against IL-6 and spartalizumab is a second generation PD-1 inhibitor.

Update: The XL888 + pembrolizumab study mentioned in the article is also moving along, presented by Mehmet Akce at the Gastrointestinal Cancers Symposium.

Posted on by Quinn Eastman in Cancer Leave a comment

Setting the goalposts for ALS clinical trials

In the fight against a relentless neurodegenerative disease such as ALS (amyotrophic lateral sclerosis), a critical question for research is: what is the definition of success?

Emory neurologists, with advice from other experts, have created a new disability rating scale for ALS. This is a set of questions patients or their caregivers answer to gauge how much ALS is eroding someone’s ability to manage daily life. The researchers think it can become a resource for testing new treatments for ALS in clinical trials.

The research used to develop the new rating scale was published on December 30 in JAMA Neurology. The rating scale itself will be available on the Emory ALS Center web site.

ALS’s attack on motor neurons makes it progressively more difficult to accomplish tasks such as household chores, daily hygiene, and eventually speaking and eating. Some patients live a year or two after diagnosis, some live ten.

Christina Fournier, MD

“If our goal in clinical trials is to have that decline happen more slowly, how we measure it matters,” says lead author Christina Fournier, MD, assistant professor of neurology at Emory University School of Medicine and co-director of Emory’s ALS Center.

Update: see Fournier’s comments to Medscape/Reuters Health here.

The current standard outcome measure is the ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised). While widely accepted in the field, the ALSFRS-R has some uneven aspects, or nonlinear weighting, which become problems when it is used to determine drug approval.

One example: a patient’s score will decline 3 points if they change from climbing stairs normally to holding a handrail, and will decline the same amount if they change from normal dressing and hygiene to being unable to dress or perform hygiene tasks without assistance. So 3 points can represent small or large changes in their lives. Also, the ALSFRS-R can change depending on symptom management, rather than underlying biology.

To put this in perspective, the most recent drug to be approved by the FDA (edaravone) displayed an effect size of 2.5 points – and the same drug faced resistance from European regulators. According to the Wall Street Journal, about 20 drugs are in clinical testing for ALS and 5 are in the late stages of development. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

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 by Quinn Eastman in Immunology, Neuro Leave a comment

Mulligan WABE interview on Ebola vaccine research

A recent WABE “Closer Look” interview with Mark Mulligan, executive director of the Emory Vaccine Center’s Hope Clinic, covers a lot of ground. It starts off with a segment — also aired on Marketplace — from reporter Michell Eloy, who visited the Hope Clinic’s lab. We hear a machine processing blood samples from a study testing an experimental Ebola vaccine and a roundup of Ebola vaccine developments.

We also hear from Carl Davis, postdoc in Rafi Ahmed’s lab, who is part of the DARPA-funded team research project studying the utility of antibodies from Ebola survivors. [Other recent news on this topic from The Scientist.]

Then, reporters Rose Scott and Jim Burress discuss several different Ebola vaccines with Mulligan. One is based on chimpanzee adenovirus, was tested at the Hope Clinic and elsewhere in the USA and the UK, and then in Liberia. While this vaccine was safe and it appears to stimulate the immune system appropriately, the outbreak fizzled out (a good thing!) before it was possible to tell if the vaccine protected people from Ebola infection. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Alzheimer’s drug discovery: looking under the right ROCK

Developing drugs that can change the progression of Alzheimer’s disease is a huge challenge. In the last few years, more than one pharmaceutical firm have abandoned clinical programs in Alzheimer’s that once looked promising. Still, Emory and Scripps scientists have found an approach that deserves a second look and more investigation.

One straightforward drug strategy against Alzheimer’s is to turn down the brain’s production of beta-amyloid, the key component of the disease’s characteristic plaques. A toxic fragment of a protein found in healthy brains, beta-amyloid accumulates in the brains of people affected by the disease.

The enzyme that determines how much beta-amyloid brain cells generate is called BACE (beta-secretase or beta-site APP cleaving enzyme). Yet finding drugs that inhibit that elusive enzyme has been far from straightforward.

Now researchers  have identified a way to shut down production of beta-amyloid by diverting BACE to a different part of the cell and inhibiting its activity. The results were published this week in Journal of Neuroscience. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Dealing with huff-puff? Think HFpEF

For this month’s Current Concept feature, we would like to explain a term from cardiology that is likely to become more prominent:

“Heart failure with preserved ejection fraction” (abbreviated as HFpEF and pronounced “heff-peff”).

Javed Butler, MD, an Emory expert on heart failure and deputy chief science officer for the American Heart Association, laid out in a recent seminar why this category of patients is so important. Look for more from him on this topic in the future.

Three points:

  1. The number of HFpEF patients is growing and they now make up the majority of patients with heart failure in the United States.
  2. No treatments have been proven to benefit them, in terms of reducing mortality.* In clinical studies, medications such as ACE inhibitors, angiotensin receptor blockers and beta-blockers have not helped.
  3. Once hospitalized, HFpEF patients have a high rate of readmission to the hospital within 30 days. The federal Medicare program is penalizing hospitals that have high rates of readmissions and heart failure is one of the largest contributors to readmissions.

The symptoms that drive people with HFpEF to the hospital are mainly fatigue and dyspnea, or shortness of breath, along with fluid in the lungs and swelling of the limbs. Along with heart failure, HFpEF patients often have conditions such as hypertension, anemia, diabetes, kidney disease or sleep apnea. Read more

Posted on by Quinn Eastman in Heart Leave a comment

Fragile X clinical trials: this is not the end

A clinical trial testing a therapy for children with fragile X syndrome is closing down, after the sponsoring company announced that the drug, called arbaclofen, was not meeting its goals.

Readers of Emory Health magazine may remember Samuel McKinnon, an arbaclofen study participant who was featured in a 2012 article and video (below).

“We were surprised,” Samuel’s mother Wendy told us Monday. “But we knew going in that there were no guarantees.”

She reports that Samuel has made significant progress in the last couple of years. He likes playing and talking with the family’s new puppy, Biscuit. Samuel’s language skills have Ray Ban outlet blossomed and he will be headed to second grade this fall. But it’s hard to say whether that’s mainly because of the experimental drug or because Samuel has been continuing to grow and work hard in school and in therapy, she says.

A sizable fraction of patients in the study appeared to benefit from the drug, just not the majority of them, says Emory genetics chair Steve Warren.

Read more

Posted on by Quinn Eastman in Neuro 2 Comments