Alzheimer’s disease (AD) is a devastating neurodegenerative disease for which there is no effective long-term treatment. “We’re beginning to learn about what might cause AD and that’s enabling us to identify druggable targets of great potential,” said Paolo Paganetti. Accumulation of a protein called beta-amyloid (Aβ) in neurons of the brain correlates with the onset and progression of AD. Aβ is derived from a protein called β-amyloid precursor protein by the action of two proteases, γ- and β-secretase.
β-Secretase, also called β-amyloid precursor protein cleaving enzyme, or BACE, has become the target of choice for Paolo and NIBR, and also for other pharmaceutical companies. Paolo loves a challenge and staying ahead of the competition is one of them. “Our compounds are novel, non-peptidic small molecule BACE inhibitors and we’re certainly among the leaders, if not the leader, in developing these drugs,” said Paolo. Assembling the BACE Project Team and recruiting expertise inside and outside of Novartis to keep the project moving gave Paolo a great deal of satisfaction.
The BACE Project will soon enter the next phase. Paolo is working closely with the Translational Medicine group in designing proof of concept (PoC) studies in man. The goal of these studies is to determine at an early stage whether a compound has the expected effect when administered to patients. “If the PoC studies are successful, we’ll be more confident that our BACE inhibitor will be effective in later stage clinical trials that will finally tell us if we have an effective treatment for AD,” said Paolo. If so, then there will be many elderly people and their families who will be very thankful.
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