An intranasally delivered peptide drug ameliorates cognitive decline in Alzheimer transgenic mice.
Yu-Sung ChengZih-Ten ChenTai-Yan LiaoChen LinHoward C-H ShenYa-Han WangChi-Wei ChangRen-Shyan LiuRita P-Y ChenPang-Hsien TuPublished in: EMBO molecular medicine (2017)
Alzheimer's disease (AD) is the most common neurodegenerative disease. Imbalance between the production and clearance of amyloid β (Aβ) peptides is considered to be the primary mechanism of AD pathogenesis. This amyloid hypothesis is supported by the recent success of the human anti-amyloid antibody aducanumab, in clearing plaque and slowing clinical impairment in prodromal or mild patients in a phase Ib trial. Here, a peptide combining polyarginines (polyR) (for charge repulsion) and a segment derived from the core region of Aβ amyloid (for sequence recognition) was designed. The efficacy of the designed peptide, R8-Aβ(25-35), on amyloid reduction and the improvement of cognitive functions were evaluated using APP/PS1 double transgenic mice. Daily intranasal administration of PEI-conjugated R8-Aβ(25-35) peptide significantly reduced Aβ amyloid accumulation and ameliorated the memory deficits of the transgenic mice. Intranasal administration is a feasible route for peptide delivery. The modular design combining polyR and aggregate-forming segments produced a desirable therapeutic effect and could be easily adopted to design therapeutic peptides for other proteinaceous aggregate-associated diseases.
Keyphrases
- cognitive decline
- mild cognitive impairment
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- clinical trial
- endothelial cells
- ejection fraction
- randomized controlled trial
- traumatic brain injury
- amino acid
- working memory
- study protocol
- photodynamic therapy
- peritoneal dialysis
- adverse drug
- phase iii
- drug induced
- pluripotent stem cells