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GSK invests in Alector’s antibodies for neurodegenerative diseases

The antibodies boost progranulin, a protein that could help treat frontotemporal dementia, Alzheimer’s disease, and more

by Ryan Cross
July 8, 2021 | A version of this story appeared in Volume 99, Issue 25


A photo of a pharmaceutical research lab.
Credit: Alector
Alector's labs in South San Francisco

GlaxoSmithKline is making a foray into neuroscience research by striking a deal worth up to $2.2 billion with the immunoneurology company Alector. The firms will co-develop two of Alector’s antibody therapies that could treat multiple neurodegenerative diseases, including Alzheimer’s disease.

GSK, which does not have many investments in drugs for neurological diseases, says the deal is part of an R&D strategy focusing on the intersection of genetics and the immune system. GSK will pay Alector $700 million upfront and up to $1.5 billion in future payments.

The partnership was announced just weeks after the controversial approval of Aduhelm, Biogen’s antibody therapy for Alzheimer’s. Although the drug lowered telltale amyloid-β plaques in the brain, Biogen’s clinical trials yielded conflicting results about the drug’s ability to actually stall cognitive decline.

Disappointments with amyloid-lowering drugs have led some companies, including Alector, to focus on new strategies for combating Alzheimer’s.

Alector’s antibodies both block sortilin, a receptor that helps remove and degrade a protein called progranulin. Progranulin is important for regulating immune responses, lysosomal function, and neuronal survival in the brain, and mutations in the progranulin gene are associated with brain cell loss and dementia. Alector has shown that blocking sortilin temporarily boosts progranulin levels.

One of the antibodies, AL001, is in a Phase 3 trial for frontotemporal dementia caused by mutations in the progranulin gene and a Phase 2 study for a different form of frontotemporal dementia. The companies plan to start a Phase 2 trial of the antibody in people with amyotrophic lateral sclerosis this year.

Alector is also testing the safety of a second sortilin-targeting antibody, AL101, in a Phase 1a trial, with plans to ultimately test the progranulin-boosting strategy in people with Alzheimer’s or Parkinson’s disease.

In addition to its programs with GSK, Alector has a partnership with AbbVie to develop antibodies for Alzheimer’s that enhance the activity of microglia, helpful immune cells in the brain.



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