Novel Peptide Inhibitors for Alzheimer’s disease

Notch‑Sparing Modulation of γ‑Secretase by Three‑Finger Toxins

Overview

　Amyloid-β (Aβ) accumulation is a key driver of Alzheimer’s disease (AD). While γ-secretase inhibitors (GSIs) have long been pursued as therapeutics, safety issues have prevented their clinical adoption.
　Using AlphaFold2–based in-silico screening, the inventors discovered that Three-Finger Toxins (3FTXs)—disulfide-rich peptides from snake venom—potently block γ-secretase–mediated APP processing. Strong inhibitory activity was confirmed in both yeast-based assays and a β-galactosidase reporter system.
　Brain-targeted AAV vectors for 3FTX expression are currently under development, with evaluation in AD model mice planned.
　Acting at sites distinct from traditional GSIs, 3FTXs offer a novel and promising approach for AD prevention and treatment.

3FTXs Exhibit Strong γ-Secretase Inhibitory Activity

Product Application

・Therapeutic and preventive agents for Alzheimer’s disease
・Potential disease‑modifying therapy targeting APP processing

IP Data

IP No.　 ： WO2024/004231　
Inventor ： E. Futai, R. Sakakibara, M. Seki, M. Hidaka, T. Ogawa
keyword ： Therapeutics, Dementia, Aβ, Alzheimer'sdisease, GSI, peptide, Venomics