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Of Mice Not Men: Promising sepsis remedy; lack of sleep linked to heart problems

This is a recurring column on early-stage research in animals or other laboratory models that have not entered the clinic yet but could have implications for future research and development of human medicines.

Promising new sepsis treatment

Research into an experimental therapy for sepsis has shown that a drug being developed at the Royal College of Surgeons in Ireland, or RCSI, has the potential to stop sepsis-causing bacteria from triggering organ damage.

Results of the pre-clinical trial of InnovoSep showed the treatment is also able to halt the blood poisoning from spreading to multiple organ failure, according to the RCSI's Sinéad Hurley, a postdoctoral fellow at the School of Pharmacy and Irish Centre for Vascular Biology.

Sepsis, otherwise known as blood poisoning, is often difficult to diagnose due to its rapid onset and because symptoms of the infection mimic those of the common flu: high temperature, rapid heart rate, rapid breathing, pain, pale or mottled skin, and feeling generally very sick. Sepsis can be caused by minor infections on the skin — like a cut or scrape — or more serious ailments including urinary tract infections, pneumonia or appendicitis.

"Sepsis occurs when an infection gets into the bloodstream and our own body's defense system spins out of control trying to fight the infection, which results in multiple organ failure if untreated," said Steve Kerrigan, Associate Professor in Pharmacology at RCSI and inventor of InnovoSep. "There is only a short window of opportunity for treatment of sepsis with the early administration of antibiotics and fluid."

However, antibiotics are often ineffective due to drug resistance or a delay in identifying the type of bacteria that has caused the infection, highlighting the need for an alternative therapy that can be used at all stages of infection against all bacterial causes of sepsis, he said. The incidence of sepsis is growing by 8% a year, according to the World Sepsis Alliance.

Sleep deficiency linked with heart disease

A lack of sleep can lead to an increased risk of heart disease and other health conditions, according to recent research carried out on mice that had been genetically engineered to develop atherosclerosis.

Researchers at Harvard Medical School and Massachusetts General Hospital repeatedly disrupted the sleep cycles of half the mice and left the other half to sleep normally. After 16 weeks, the sleep-disrupted mice developed larger arterial plaques and had twice the level of certain white blood cells; they also had lower amounts of hypocretin, a hormone made by the brain that plays a key role in regulating sleep, suggesting hypocretin loss during disrupted sleep contributes to inflammation and atherosclerosis.

"We've identified a mechanism by which a brain hormone controls production of inflammatory cells in the bone marrow in a way that helps protect the blood vessels from damage," lead researcher Filip Swirski said in a news release. "This anti-inflammatory mechanism is regulated by sleep, and it breaks down when you frequently disrupt sleep or experience poor sleep quality."

"It's a small piece of a larger puzzle," he said.

High blood pressure may increase risk of dementia in later life

Studies suggest that high blood pressure, which is a leading risk factor for heart disease, stroke and kidney failure, may increase the risk of cognitive impairment and dementia later in life.

In the Sprint trial, more than 9,300 adults at least 50 years old were randomly assigned to an intensive treatment or a standard treatment and observed over 3.3 years. Participants were at high risk for cardiovascular disease but had no history of stroke or diabetes at the start of the trial.

Within the trial, a separate assessment dubbed Sprint Mind aimed to address whether intensive blood pressure control would reduce the risk of developing dementia and mild cognitive impairment.

The researchers, led by Jeff Williamson at the Wake Forest School of Medicine, found that there were fewer dementia cases diagnosed in the intensive treatment group, although the difference was not large enough to prove it did not happen by chance. Their results, published in JAMA on Jan. 28, also found that the intensive treatment was safe for the brain and appeared to reduce the risk of mild cognitive impairment by about 20%.

Still, as the blood pressure management study was stopped early, this may have weakened the ability to detect differences in dementia cases between the two groups.

"The fact that there was still an MCI result when the study was cut short makes these results encouraging," said Laurie Ryan of the U.S. National Institute of Ageing's division of neuroscience. "Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear."