Anxiety disorders

Selective anxiolysis produced by ocinaplon, a GABAA receptor modulator. Lippa, A. et al. Proc. Natl Acad. Sci. USA 102, 7380–7385 (2005)

Individuals with anxiety disorders are commonly prescribed benzodiazepines, which act via GABAA (γ-aminobutyric acid A) receptors but cause side effects such as sedation, muscle relaxation and ataxia. Compounds with selectivity for type I receptors have been shown to elicit anxiolytic effects at lower concentrations than those producing benzodiazepine-type side effects in animals. Lippa et al. report a compound, ocinaplon, which is anxio-selective in humans. A double-blind placebo-controlled trial of at least 40 patients showed that a 2-week regimen of ocinaplon caused a significant reduction in scores from the Hamilton rating scale for anxiety with no benzodiazepine-like side effects.

HIV

Antigenic conservation and immunogenicity of the HIV coreceptor binding site. Decker, J. M. et al. J. Exp. Med. 201, 1407–1419 (2005)

Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Trkola, A. et al. Nature Med. 48, 3122–3125 (2005)

Two papers on HIV published recently provide insights into the potential of treating the infection with neutralizing antibodies or vaccines. Decker et al. provide new information about the immunogenicity of the HIV-1 envelope glycoprotein and suggest that, in contrast to previous reports, the co-receptor-binding site on HIV-1 is strongly immunogenic and elicits high titres of antibody that neutralize HIV-1 as well as multiple strains of HIV-2. Their results will aid the development of neutralization assays for HIV vaccine assessment. In the second paper, Trkola et al. studied the ability of the humoral immune response to delay HIV-1 rebound after withdrawal of antiretroviral therapy. They found that passive immunization with neutralizing antibodies had little effect in delaying viral rebound in patients with chronic infections, whereas those acutely infected fared better. The antibody 2G12 was found to be crucial to the activity of the neutralizing antibody cocktail in vivo.

Gene expression

MicroRNA expression profiles classify human cancers. Lu, J. et al. Nature 435, 834–838 (2005)

MicroRNAs (miRNAs) are a class of small non-coding RNAs with diverse regulatory functions. In this paper, Lu et al. provide evidence that miRNAs have unexpected diagnostic potential in cancer. A bead-based flow cytometry miRNA-expression profiling method was developed to perform a systematic expression analysis of 334 different human cancer samples using 217 mammalian miRNAs. The majority of miRNAs had lower expression in tumours than in normal tissue, and hierarchical clustering reflected both developmental lineage and differentiation state of tumours. Moreover, when used to classify poorly differentiated tumours, miRNA expression was far more accurate than conventional mRNA profiling. Unlike mRNAs, miRNAs remain intact in formalin-fixed paraffin sections, and so this method might be easily implemented in the clinic.