7:19 PM
 | 
Jan 18, 2018
 |  BC Innovations  |  Strategy

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 -- is showing a shift as well. While 38-47% of projects in the last five years still focus on β amyloid or tau, 227 of the 396 (57%) projects in AD are on other pathways (see “Funding for Alzheimer’s”).

Much of the new activity is based on emerging strategies such as systems biology as well as data from large-scale genomics studies.

Laurie Ryan, chief of the Dementias of Aging Branch of NIH’s National Institute on Aging (NIA) said NIH is betting systems biology approaches can begin to construct molecular networks that contribute to disease onset or progression, and help pinpoint druggable targets within them.

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.

NIH’s Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD) Target Discovery and Preclinical Validation Project, launched in 2014, is backing systems biology studies that aim to integrate the large quantity of -omics and imaging data that has been generated from patients.

Other funders and investors are also pushing the field toward new targets.

Kate Bingham, a managing partner at SV Health Investors, told BioCentury the firm’s Dementia Discovery Fund (DDF) is only backing companies outside of the β amyloid space. DDF has raised at least $150 million since its launch in 2015.

“Our view is there are lots of drivers of the disease,” she said. “Our fund was set up to look at different areas of biology that are genetically rich, where there is evidence of causative biology, and where you can start to identify different patient cohorts that would be linked to that causative biology.”

Timothy Armour, president and CEO of the Cure Alzheimer’s Fund, told BioCentury his organization...

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