June 1, 2013

Lab Notes: Stop Hepatitis C from Multiplying

By MedPage Today Staff

Published: May 31, 2013

Hep C may be thwarted by muting its ability to replicate. Also this week: a promising approach to preserve muscle in ALS, and the body's microbiota fight a sexually-transmitted disease.

Stopping HCV in Its Tracks

Researchers have identified a possible new approach to stopping hepatitis C virus (HCV) infection that involves attacking the virus's ability to reproduce.

The attack was brought by agents called RNA aptamers, which work by binding to and disabling the NS5B replicase enzyme involved in replication of the virus.

As Seong-Wook Lee, PhD, of Dankook University in South Korea, and colleagues reported in the Journal of Virology, the agents inhibited replication of two variants of HCV -- genotypes 1b and 2a -- in cultured human liver cells without inducing toxicity or innate immunity. Also, there were no signs that the approach induced resistance.

The aptamers were then modified for in vivo availability and liver-specific delivery. When administered intravenously to mice, the aptamers entered liver tissue at concentrations that suggested therapeutically effective quantities could be achieved in human patients.

-- Todd Neale

Growth Factors Preserve Muscle in ALS

Implanting human stem cells into the leg muscles of a rat model of amyotrophic lateral sclerosis (ALS) led to delay in disease onset, preservation of muscle function, and longer survival, researchers from the University of Wisconsin reported.

Masatoshi Suzuki, PhD, and colleagues performed a series of experiments in which stem cells that release specific growth factors were injected into the neuromuscular junction, where the neurons attach to the muscles in the leg.

These growth factors, glial cell line-derived neurotropic factor and vascular endothelial growth factor, together had synergistic effects in preserving motor function and survival in the animals, the researchers reported in Molecular Therapy.

These stem cells and growth factors are already being used in other clinical contexts, and a clinical trial of stem cell transplantation into the spines of ALS patients is ongoing. But implanting the cells into muscles of the legs and even the diaphragm would be a simpler process if similar improvements can be demonstrated in humans, the researchers noted.

-- Nancy Walsh

Lactic Acid Bacterium Fights Trichomonas

Women have a natural bacterium that fights a sexually transmitted infection, stated researchers from the University of Auckland in New Zealand.

The parasite Trichomonas vaginalis binds to the vaginal wall and damages cells lying there. But they first must overcome "an unfavorable environment dominated by lactobacilli," which is a lactic acid bacterium, according to the study published online in the journal Sexually Transmitted Infections.

"Understanding the role that Lactobacillus plays in T vaginalis infection/disease might reveal new therapeutic approaches which include taking advantage of the natural probiotic activity of lactobacilli," the authors said.

-- Kathleen Struck

Body Clock Key to Immune Response

It may be the time of day that determines one's resistance to bacterial infections.

Up to 15% of human genes are regulated by the day-night pattern of circadian rhythms. With this in mind, Paolo Sassone-Corsi, PhD, from UC Irvine, and colleagues found that the ability of mice to fend off infection was linked to circadian-controlled genes.

Understanding the circadian genetics regulating immunity "gives us the ability to target treatments that supplement the power of the body clock to boost immune response," Sassone-Corsi said in a statement.

The study was published online in the Proceedings of the National Academy of Sciences.

-- Chris Kaiser

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