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October 21, 2016

Mutation May Explain Why Some Get More Severe RSV Disease

RSV infection may cause mild, cold-like symptoms, or more serious symptoms, leading to hospitalization and even death.
RSV infection may cause mild, cold-like symptoms, or more serious symptoms, leading to hospitalization and even death.

A mutation in the gene of a white blood cell protein contributes to the severity of respiratory syncytial virus (RSV) infection, according to a paper published in EBioMedicine by researchers at NIEHS and their collaborators. RSV contributes to bronchiolitis, pneumonia, asthma and respiratory failure. It is also the leading cause of respiratory illness in infants, immunocompromised adults and the elderly.

The team used genome-wide association studies in mice to identify candidate genes involved in RSV severity. The most promising gene, macrophage receptor with collagenous structure (MARCO), produces a protein that allows a particular type of white blood cell to fight infection. The finding was surprising because MARCO had not previously been associated with RSV.

Mice with the MARCO gene knocked out experienced more severe symptoms from exposure to RSV, compared to wild-type mice. And effects in humans are strikingly similar. In two independent populations of children, infants born with a mutated MARCO gene exhibited more severe RSV symptoms than those with the wild-type gene.

“MARCO is an immune system gene that helps clear inflammation,” said Dr. Steven Kleeberger, lead researcher on the study. “If the gene is mutated, it can’t resolve the inflammation, so cells and mucus remain in the lung, blocking the airway.”

Using information learned from mouse and human studies, the team hopes to develop a diagnostic tool to identify infants subject to severe RSV disease before they get sick. There is no vaccine for RSV and some of its health effects are irreversible, so preventing even a small number of RSV-induced asthma or pneumonia cases could have a huge impact.

Targeting Cardiovascular Disease Risk Factors May Be Important Across a Lifetime

New findings suggest that all adults, including those over 65, should be mindful of risk factors for cardiovascular disease. The results, published in the Journal of the American Geriatric Society, are part of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, which looks at stroke incidence in approximately 30,000 individuals. The REGARDS study is funded by NINDS.

“As life expectancy continues to increase, we need to improve risk factor prevention and management for stroke and heart disease across the lifespan, including for those adults over the age of 65,” said one of the study authors, Dr. Claudia Moy of NINDS. “The latest findings from the REGARDS study reveal that no age group is immune to risk factors related to cardiovascular disease and that prevention efforts should target all adults.”

In the current study, researchers examined individuals over the course of 10 years to determine how many developed risk factors known to be associated with stroke and heart disease. The study included a sample of black and white Americans, with more than half of the participants living in the Stroke Belt, an area of the southeastern U.S. where stroke mortality is higher than in the rest of the country.

“In addition to improving treatment and control of potent risk factors for stroke and heart disease, finding ways to prevent development of those risk factors may be a potential strategy to lower rates of cardiovascular disease across the age span, but especially in black Americans,” said Moy.

Drug to Treat Alcohol Use Disorder Shows Promise Among Drinkers with High Stress

A new medication that targets part of the brain’s stress system may help reduce alcohol use in people with alcohol use disorder (AUD), according to a new study by researchers at NIAAA.

“Medications have become an important tool for treating alcohol use disorders, but current medications are not effective for all people with AUDs,” said NIAAA director Dr. George Koob. “We’re committed to developing new medications to provide effective therapy to a broader spectrum of people with AUDs.”

As reported online in the journal Neuropsychopharmacology, researchers led by Dr. Raye Litten, acting director of NIAAA’s Division of Medications Development, conducted a randomized clinical trial of a new compound called ABT-436, which is designed to block the effects of vasopressin, a neuropeptide produced in the hypothalamus of the brain.

“Vasopressin helps to regulate the pituitary adrenal axis and other brain circuits involved in emotion,” explained Litten. “As such, it plays a role in regulating stress, anxiety and their interaction with AUD.”

Researchers found that participants receiving ABT-436 experienced more days of alcohol abstinence than those receiving the placebo. In particular, participants who reported high levels of stress appeared to respond better to ABT- 436, in that both the frequency of their drinking and the number of heavy drinking days they experienced decreased.

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