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KVAL: Mitophagy induction to treat Alzheimer’s disease – a hit-to-lead drug discovery project

Awarded: NOK 0.50 mill.

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2022 - 2023

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is characterized by memory loss, cognitive impairment, and functional decline. The number of prevalent cases of AD is high and is expected to grow to 44 mill due to aging of the population. The current competitive landscape in AD offers medications that are aimed at treating the symptoms of the disease, which are modestly effective and primarily off patent. High unmet need, large market and few approved effective drugs make AD a very commercially attractive space for a drug development program. The Evandro Fei Fang group at the University of Oslo was one of the very first research teams to propose defective mitophagy as a key driver in AD initiation and progression. They have demonstrated the effectiveness of mitophagy induction in inhibiting memory loss in multiple AD animal models. Fang’s lab has worked extensively with mitophagy inducers as anti-AD drug candidates, and recently they identified a new mitophagy inducer, JGX-1. JGX-1 is a diterpene plant-based compound that can be extracted from Croton crassifolius Geisel. The aim of this qualification project is to do medicinal chemistry work to establish the viability and optimal starting point for a drug development path based on JGX-1 or a close analogue. This qualification project will lead to a follow-on verification application to fund the chemical derivatization process. A successful verification project would be expected to culminate in a lead compound with in vivo PoC supporting licensing negotiations with the pharmaceutical industry.

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