Eye Disorders

Pegaptanib for neovascular age-related macular degeneration. Gragoudas, E. S. et al. N. Engl. J. Med. 351, 2805–2816 (2004).

Age-related macular degeneration (AMD) is a leading cause of severe vision loss in people older than 55 years of age in the developed world. Gragoudas et al. report the results of Phase III trials of pegaptanib, a modified RNA aptamer that binds to and blocks the activity of vascular endothelial growth factor. Pegaptanib was shown to be an effective and safe treatment for neovascular AMD; on the basis of this and other data, it has recently become the first aptamer-based therapeutic to be approved by the FDA.

Neurodegenerative disease

Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. Pedrini, S. et al. PLoS Med. 2, e18 (2005).

Recent evidence suggests that statins, which are widely used as cholesterol-lowering drugs, might be associated with a decreased risk for Alzheimer's disease. The underlying mechanisms are poorly understood, but one idea is that statins modulate the metabolism of amyloid precursor protein, which has a key pathogenic role in Alzheimer's disease. Pedrini and colleagues provide data that indicate that statins exert these effects by modulating the isoprenoid pathway and Rho-associated protein kinase 1 (ROCK1).

Screening

ALARM NMR: a rapid and robust experimental method to detect reactive false positives in biochemical screens. Huth, J. R. et al. J. Am. Chem. Soc. 127, 217–224 (2005).

Reactive compounds are a major source of costly and time-consuming false positives in high-throughput screening. To address this issue, Huth and colleagues have developed a rapid and reliable method based on nuclear magnetic resonance for identifying reactive compounds, which they show could significantly augment current in silico approaches.

Infectious diseases

IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART. Wang, F. X. et al. J. Clin. Invest. 115, 128–137 (2005).

The persistence of HIV-1 in virally suppressed infected individuals being treated with highly active antiretroviral therapy (HAART) is a key problem in disease treatment. The addition of T-cell-activating agents has been proposed as a potential strategy to purge the pool of 'latently infected' cells. Wang et al. show that interleukin-7 upregulated the expression of HIV-1 in latently infected cells from HIV-1 patients on suppressive HAART more effectively than previous agents tested, and so might be a valuable component of novel immune-antiretroviral approaches.