TY - JOUR T1 - Local inhibition of IL-4 and IL-13 protects lung function in OVA mouse model JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p958 AU - Nicole Stowell AU - Michael Baumann AU - Sandra Bruckmaier AU - Andreas Cornelius AU - Colleen Kane AU - Cassandra Lowenstein AU - Kristen Picha AU - Gaby Sennhauser AU - Edward Yurkow AU - Zhao Zhou AU - Michael Stumpp AU - Karyn O'Neil Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p958.abstract N2 - DARPinsTM (Designed Ankyrin Repeat Proteins) are a novel class of proteins that combine the affinity and specificity properties of antibodies with the solubility and tissue penetration properties of small molecules. The excellent biophysical properties of DARPin domains allows for simple engineering of multispecificity by linking domains that target different ligands. DARPin134 is a bispecific DARPin that inhibits binding of murine IL-13 and IL-4 to their receptors.The bispecific molecule (DARPin134) or either of the mono-specific molecules was delivered to the lungs of mice via intra-tracheal instillation during an acute ovalbumin sensitization and challenge model. Free IL-4 and IL-13 levels were reduced in the BAL following treatment with DARPin134. While the anti-IL-4 and anti-IL-13 DARPins each showed a trend towards reducing eosinophils in the lungs of mice, the bi-specific DARPin significantly reduced eosinophil infiltration. In addition, an improvement airway hyper-responsiveness in mice treated with DARPin134 was observed.A variety of studies have confirmed the unique and overlapping roles for IL-13 and IL-4 in the pathology of asthma. Molecules inhibiting IL-4 alone have failed in clinical trials of asthma and a variety of clinical studies with molecules targeting IL-13 are ongoing. In contrast, DARPin134 targets both IL-4 and IL-13 and in vitro data demonstrate the bispecific DARPin has high potency, affinity and excellent biophysical properties. Blockade of both IL-4 and IL-13 in the pulmonary compartment could provide a therapeutic option in pulmonary diseases without disruption of either cytokine systemically. ER -