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news.Scientists at TorreyPines Therapeutics have identified compounds that lower levels of A-Beta42, a neurotoxic peptide associated with Alzheimer's disease, without inhibiting protein processes that are vital for normal body function.
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Data on compounds from Series591 showed that oral administration of several compounds within the series lowered A-Beta42 levels in the plasma and brain of Alzheimer’s disease mouse models.
To date, all agents that have decreased the peptides A-Beta40 and A-Beta42, have also decreased Notch processing. The Series591 compounds have novel structural features and appear to modulate, rather than inhibit gamma-secretase activity.
“A growing body of research supports the notion that two peptides found in the brain, A-Beta40 and A-Beta42, are toxic to neurons and are the causative pathogenic agents in Alzheimer’s disease,” said Dr Steven Wagner, chief scientific officer of TorreyPines. “Unlike other modulators of gamma-secretase activity, our Series591 compounds lower A-Beta42 levels without inhibiting Notch proteolytic processing which is vital to support normal vascular and immunological functions.”