title: Wheat germ agglutinin enhanced cerebral uptake of anti-Aβ antibody after intranasal administration in 5XFAD mice.
abstract: Alzheimer's disease (AD) is the 6th leading cause of death in United States afflicting >5 million Americans. This number is estimated to triple by the middle of the century if effective treatments are not discovered. Current therapy for AD is mainly symptomatic. Effective disease-modifying treatments are needed that would eliminate the cause rather than the symptoms of the disease. Polymerization of monomeric beta-amyloid peptide (Aβ) into dimers, soluble oligomers and insoluble fibrils is considered the prime causative factor in triggering AD pathogenesis. Based on these facts, removal/reduction of Aβ has gained importance as a primary therapeutic target in treating the cause of the disease. In that regard, passive immunotherapy with direct delivery of anti-Aβ antibodies to the brain has shown great promise, but awaits the challenge of overcoming greater influx of anti-Aβ antibody into the brain. This investigation was undertaken to maximize direct delivery of immunotherapeutics to the brain by using wheat germ agglutinin (WGA) as a novel axonal transporter-carrier to be conjugated with anti-Aβ antibody (6E10) raised against EFRHDS 3-8 amino acid (aa) epitopes of Aβ known to react with 1-16 aa residues of mono-/di-/oligomeric Aβ. This is the first report showing the use of WGA as an efficient axonal transporter carrier that not only enhanced the influx of anti-Aβ antibody directly into the brain but also resulted in greater reduction of cerebral Aβ compared to the unconjugated anti-Aβ antibody delivered intranasally in Alzheimer's 5XFAD model.
authors.affiliation: Neuroscience Research, Jesse Brown VA Medical Center, Chicago, IL 60612, USA. nchauhan@uic.edu
authors.forename: Neelima B
authors.initials: NB
authors.lastname: Chauhan
authors.forename: Francesca
authors.initials: F
authors.lastname: Davis
authors.forename: Chun
authors.initials: C
authors.lastname: Xiao
mesh_terms: D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000276:immunology* / Q000628:therapy*; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D014909:Wheat Germ Agglutinins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000906:Antibodies; D014909:Wheat Germ Agglutinins