Thanks Jim - very useful perspective.
On another topic, did you see this? (the relevant anti-p40 drug is from JNJ and is approved to treat psoriasis)
NATURE MEDICINE | ARTICLE
Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline Johannes vom Berg, Stefan Prokop, Kelly R Miller, Juliane Obst, Roland E Kälin, Ileana Lopategui-Cabezas, Anja Wegner, Florian Mair, Carola G Schipke, Oliver Peters, York Winter, Burkhard Becher & Frank L Heppner Affiliations Contributions Corresponding authorsNature Medicine (2012) doi: 10.1038/nm.2965Received 05 July 2012 Accepted 05 September 2012 Published online 25 November 2012
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Abstract
Abstract Author information Supplementary informationThe pathology of Alzheimer's disease has an inflammatory component that is characterized by upregulation of proinflammatory cytokines, particularly in response to amyloid-ß (Aß). Using theAPPPS1 Alzheimer's disease mouse model, we found increased production of the common interleukin-12 (IL-12) and IL-23 subunit p40 by microglia. Genetic ablation of the IL-12/IL-23 signaling molecules p40, p35 or p19, in which deficiency of p40 or its receptor complex had the strongest effect, resulted in decreased cerebral amyloid load. Although deletion of IL-12/IL-23 signaling from the radiation-resistant glial compartment of the brain was most efficient in mitigating cerebral amyloidosis, peripheral administration of a neutralizing p40-specific antibody likewise resulted in a reduction of cerebral amyloid load in APPPS1 mice. Furthermore, intracerebroventricular delivery of antibodies to p40 significantly reduced the concentration of soluble Aß species and reversed cognitive deficits in aged APPPS1 mice. The concentration of p40 was also increased in the cerebrospinal fluid of subjects with Alzheimer's disease, which suggests that inhibition of the IL-12/IL-23 pathway may attenuate Alzheimer's disease pathology and cognitive deficits. |
