Tumor necrosis factor (TNF)-α inhibitors (TNFI) are a major class of  biologic therapeutics, and include decoy receptor and monoclonal antibody  (MAb) therapeutics that block TNFα action.  TNFα is a pro-inflammatory cytokine  in brain disease, such as stroke, brain or spinal cord injury, or Alzheimer’s  disease. However, the biologic TNFIs cannot be developed for the brain, because  these large molecules do not cross the blood-brain barrier (BBB).  Brain  penetrating forms of TNFα decoy receptors or anti-TNFα antibody therapeutics  can be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse,  such as the MAb against the human insulin receptor (HIR).  The HIRMAb  undergoes receptor-mediated transport across the BBB via the endogenous  insulin receptor, and carries into brain the fused biologic TNFI.  A fusion protein  of the HIRMAb and the type II TNF receptor (TNFR) extracellular domain,  designated the HIRMAb-TNFR fusion protein, has been engineered and expressed  in stably transfected Chinese hamster ovary (CHO) cells. The HIRMAb-TNFR  fusion protein binds both the HIR and TNFα with low nM affinity.  The HIRMAb  cross reacts with the Rhesus monkey insulin receptor, and the HIRMAb-TNFR is  rapidly, and selectively, taken up by primate brain at concentrations that inhibit  TNFα.  In addition, a fusion protein of the HIRMAb and a therapeutic single chain  Fv (ScFv) antibody has been engineered and also expressed in stably transfected  CHO cells.  The BBB molecular Trojan horse platform technology allows for the  engineering of brain-penetrating recombinant proteins as new biologic  therapeutics for the human brain.