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The next wave in neurodegeneration expands beyond neurons

Why modulating microglia could give drug developers a new handle on neurodegeneration

Working in the background, while amyloid therapies have floundered, has been a group of companies betting that the immune system can do for neurodegeneration what it is has done for oncology. The first wave of these companies is moving into early stage trials with therapies that modulate microglia, the brain’s immune cells, and the first data could come by year end.

As the immune system is increasingly implicated in all areas of disease, the neurodegeneration field is hoping for a paradigm shift analogous to the one that all but turned oncology into immuno-oncology.

The hope is pinned on genetic data, where the strongest evidence comes from Alzheimer’s disease.

“About 50% of genes discovered and linked to Alzheimer’s disease point specifically to glial biology and even more specifically to microglia,” said Ryan Watts, CEO of neurology-focused Denali Therapeutics Inc.

A major influence came from a 2012 paper that pinpointed TREM2 as a top genetic risk factor for AD, based on evidence tying it to a loss-of-function mutation in the gene.

The paper sparked a flood of venture and public capital into microglia-centric biotechs, with five companies, three of which were new, raising $1.3 billion since 2013 (see Figure: “Neuroinflammation Fundraising”).

Figure: Neuroinflammation fundraising

Companies focused on microglia and neuroinflammation have raked in cash in recent years, led by the $287 million IPO by Denali Therapeutics Inc. (NASDAQ:DNLI) in 2017. Alector Inc. (NASDAQ:ALEC) raised $175.8 million in its 2019

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