Author(s): Rita PY Chen
The pathological hallmarks of Alzheimer’s disease (AD) are the deposition of extracellular senile plaques resulting from amyloid-β (Aβ) peptide aggregation, the formation of intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, and extensive neuron death. Although 110 years have passed since the discovery of AD, the field still debates whether the amyloid hypothesis or tau hypothesis is the key issue in AD therapy. The issue of population aging makes the prevention or therapy of AD a pressing issue since the onset of this disease is highly age-correlated. Over the past two decades, the number of AD-related publications per year has grown rapidly, but to no avail. The failure rate of anti-AD clinical trials is ~99.9% and only cholinergic drugs for symptomatic control are available in the market. The success of the phase 1b clinical trial of Aducanumab immunotherapy in 2014 rekindled interest in anti-amyloid therapy, whereas the failure of the phase 3 clinical trial of Solanezumab immunotherapy once again quashed the optimism. Recently, a peptide therapy for AD was developed. A polyethylenimine (PEI) conjugated peptide, V24P(10-40)- PEI, was proposed to serve as a scavenger by trapping endogenous Aβ produced in the brain to avoid the formation of toxic aggregates. Most importantly, this peptide was given as a nose drop. After treating the AD double transgenic mice APP/PS1 with V24P(10-40)-PEI for four months, there was a significant reduction in Aβ accumulation in the brains of the treated mice. V24P(10-40)-PEI was designed to trap Aβ to interfere with its self-association, which renders Aβ more vulnerable to the attack of various endogenous Aβ-degrading enzymes.
