Therapeutics: Dickkopf homolog 1 (DKK1)

Mouse studies suggest DKK1 inhibitors could help treat allergic asthma and cutaneous leishmaniasis. Blood levels of DKK1 were higher in a mouse model of dust mite allergen-induced asthma than in normal mice. In the asthma model, DKK1 knockout decreased airway resistance, lung inflammation and leukocyte infiltration to the lung compared with normal DKK1 expression. Also in the model, a DKK1 inhibitor tool compound decreased neutrophil recruitment to the lung, and levels of allergen-specific T cells and T helper type 2 (Th2) cytokines in the lungs compared with no treatment. In a mouse model of cutaneous Leishmania major infection, the DKK1 inhibitor decreased lesion size, parasitic burden at the site of infection and Th2 cytokine levels in draining lymph nodes compared with vehicle. Next steps could include testing DKK1 inhibitors in models of other diseases involving Th2 inflammatory responses.

Novartis AG and MorphoSys AG have BHQ880, a HuCAL neutralizing antibody against DKK1, in Phase II testing to treat multiple myeloma (MM). ...