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Temple Street Biotech is developing a fully human monoclonal antibody targeting the cellular prion protein (PrPC) for the treatment of Alzheimer's disease and Creutzfeldt-Jakob disease (CJD). The antibody is designed to block the interaction between toxic amyloid-beta oligomers (Aβo) and PrPC, which acts as a high-affinity receptor for these oligomers on the surface of hippocampal neurons. By interrupting this binding, the antibody prevents the activation of a neurotoxic signaling cascade involving metabotropic glutamate receptor 5 (mGluR5), Fyn kinase, and protein tyrosine kinase 2 (Pyk2), which otherwise leads to synaptic loss and cognitive impairment. Preclinical data in Alzheimer's transgenic mouse models indicate that the antibody can rescue memory function and protect synapses without the need for amyloid plaque clearance.
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