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γ-secretase inhibitors inhibit Notch, a transmembrane receptor that drives many cases of T cell acute lymphoblastic leukemia—but there are safety concerns with such drugs. Combining these inhibitors with glucocorticoids could provide a more effective and safer approach (pages 50–58).
A new approach to the treatment of sepsis relies on the infusion of mesenchymal stem cells, multipotent cells used experimentally to treat a range of medical conditions. In mouse models, the cells seem to reprogram immune cells that can contribute to sepsis (pages 42–49).
Numerous drugs have been invented to counteract heart failure, but some have not lived up to their initial promise. As David Kass explains, the development of drugs to increase cardiac contractility has been particularly frustrating—but failure is also leading to new biological insights and new experimental approaches. Mark Anderson and Peter Mohler explore new ways of targeting calcium-mediated signaling in the heart—with a focus on combating heart failure by targeting 'local' forms of signaling in heart muscle.
Mental retardation and epilepsy can result from the aberrant migration of neurons during development. An experimental treatment in prenatal mice restores normal patterns of migration and eases symptoms (pages 84–90).
A trial of a childhood vaccine against a common respiratory virus went terribly wrong in the early 1960s. Instead of protecting children, the vaccine exacerbated disease in response to infection. We now have a better understanding as to why (pages 34–41).
A growing body of evidence supports the idea that some infectious diseases have a heritable component, a notion put forth by none other than Louis Pasteur. As scientists begin to catalog the genetic changes that predispose people to specific illnesses, they are also exploring how to prevent sickness by replacing the missing parts of the immune system's defensive armor. Laura Spinney reports.
