After amyloid

How the Alzheimer’s disease community is moving past amyloid

As the Alzheimer’s field is slowly taking on the search for new targets outside of the β amyloid and tau hypotheses, researchers are ramping up exploration of new pathways and looking to the disease’s genetics for clues. High on the list of emerging areas are mitochondrial factors, inflammasome targets and neuroprotection.

Moreover, lessons from oncology are driving the quest to find ways of using precision medicine to break the notion that Alzheimer’s is a single disease.

BioCentury’s analysis shows that while β amyloid and tau still pervade the landscape in both academia and industry, in early stage research, non-traditional targets now represent more than half the activity.

The picture arising from products in development, translationally relevant publications and NIH-funded projects suggests that new mechanisms are poised to enter the clinic or fuel discovery projects in the next few years.

Data from BioCentury’s BCIQ database show that 60% of Phase III and 100% of Phase II/III therapies target much-exploited targets, including β amyloid, tau or cholinergic pathway proteins, via one route or another. And β amyloid pathways alone are still the target of about one-fifth to one-third of the products in early clinical and preclinical development (see “Targeting Alzheimer’s”).

But 51% of the preclinical programs target new mechanisms, and some have started to reach the clinic - with 36% to 56% of the compounds in Phase I or II targeting proteins that work by different mechanisms.

That proportion grows earlier in the innovation pipeline. In the last five years, 62-80% of the translational opportunities in Alzheimer’s disease (AD) identified in the Distillery section of BioCentury Innovations have involved targets outside of the β amyloid, tau or cholinergic pathways (see “Distilling New Targets”). The Distillery contains discoveries from the academic literature selected for translational potential.

NIH funding -- the earliest stage of the process

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