Editors' ChoicePULMONARY DISEASES

Highlight: A new way to block the development of asthma from dust mites

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Sci. Signal.  18 Apr 2017:
Vol. 10, Issue 475, eaan3693
DOI: 10.1126/scisignal.aan3693

Targeting a transcription factor, generally considered to be “nondruggable,” may help to prevent asthma from developing.

Asthma, an inflammatory airway disease with a typical onset in childhood, is increasingly being diagnosed in inner city populations. Exposure to airborne allergens from decaying house dust mites is thought to be a major contributor to asthma development. In this issue of Science Signaling, Sun et al. identified a small molecule inhibitor of FOXM1, a transcription factor that controls critical cellular changes associated with asthma development, and a member of a broad class of molecules generally considered “undruggable.” The drug—named RCM-1 after Robert Costa, the late scientist who identified the human FOXM1 gene—markedly reduced cytokine production in the lungs, suppressed airway mucus accumulation, and markedly ameliorated both the lung tissue changes and invasion of inflammatory cells into the peribronchial space seen in mice exposed to extracts of house dust mites or interleukin-13, a proinflammatory cytokine that is central to the pathogenesis of asthma. The drug, or optimized versions of it, may be of direct benefit to patients in the early stages of asthma, and the work provides clear evidence that targeting of “nondruggable” targets such as transcription factors is both possible and promising.

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