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Flipping the Script

For years doctors have treated cardiovascular disease by trying to bring down patient's cholesterol levels. Now, some drugmakers are taking the opposite approach.

The Nature News Blog reports on a clinical trial by San Francisco-based pharmaceutical firm Resverlogix that found its BET protein inhibitor RVX-208, raised levels of high-density lipoprotein — aka "good cholesterol."

Because HDL cholesterol works in the body to lower low-density lipoprotein, or "bad cholesterol," pharma researchers hope that by bumping up levels of HDL they can decrease levels of LDL. This could provide an alternative to drugs like statins, which work by targeting LDL production directly.

Just raising HDL levels isn't enough, however. As Nature notes, Pfizer's torcetrapib showed similar effects in phase II studies, but actually worsened patient outcomes in phase III studies. This might be because while the agent caused an increase in HDL production, this new HDL didn't act in typical LDL-lowering fashion.

Resverlogix president Donald MacCaffrey hopes his company's drug will overcome this problem, pointing out that it not only increased HDL levels, but also the levels of the Apo-A1 protein HDL needs to function.

Beyond the agent's potential as a CVD treatment, it has also drawn interest due to its target, Nature says. RVX-208 goes after an epigenetic bromodomain protein, a class of molecule that has been implicated in a range of diseases including cancer and HIV.

The Scan

Germline-Targeting HIV Vaccine Shows Promise in Phase I Trial

A National Institutes of Health-led team reports in Science that a broadly neutralizing antibody HIV vaccine induced bnAb precursors in 97 percent of those given the vaccine.

Study Uncovers Genetic Mutation in Childhood Glaucoma

A study in the Journal of Clinical Investigation ties a heterozygous missense variant in thrombospondin 1 to childhood glaucoma.

Gene Co-Expression Database for Humans, Model Organisms Gets Update

GeneFriends has been updated to include gene and transcript co-expression networks based on RNA-seq data from 46,475 human and 34,322 mouse samples, a new paper in Nucleic Acids Research says.

New Study Investigates Genomics of Fanconi Anemia Repair Pathway in Cancer

A Rockefeller University team reports in Nature that FA repair deficiency leads to structural variants that can contribute to genomic instability.