CNEN

Dr. Spencer’s research focus is the 1) degradation and clearance of aggregating protein in the brain and 2) delivery of therapeutic proteins and nucleic acids for the treatment of neurodegenerative diseases.  My investigations into the accumulation and potential therapeutic targets of Aß for Alzhieimer’s disease and a-synuclein for Parkinson’s disease and other synucleinopathies has lead to a focus on the protein degradation pathway in the cell.  I have spent many years investigating the endosomal and autophagy pathway of protein degradation and found targets for therapeutics.

The second major focus of my research is the delivery of therapeutics to the CNS from the blood.  Delivery of therapeutic proteins to the brain is a significant hurdle in the translation of bench-side research to bedside treatment.  Intra-venous delivery of a recombinant protein or peptide followed by widespread distribution in the CNS is the ideal approach for many neurological disorders that require dispersed therapeutic delivery.  Recent attempts to delivery recombinant proteins and peptides to discrete structures in the CNS have met with some success using viral vector delivery or convection delivery; however, these approaches require stereotaxic injection through the skull and are likely best limited to single or few structures in the CNS.  I have characterized a 39 amino acid LDL-receptor binding domain from Apolipoprotein B that when fused to a target protein, facilitates transport from the blood to the CNS.