Therapy Type: Immunotherapy (active) (timeline)
Target Type: Inflammation (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 1)
Company: AbbVie, Alector
This antibody is being developed in a partnership between Alector and Abbvie. It binds the microglial receptor TREM2 and activates signaling, increasing phosphorylation of TREM2's downstream effector Syk. In APPPS1 mice, the antibody reportedly doubled the number of CD11b-positive microglia in cortex and hippocampus 72 hours after injection. Microglia expressed more pro-inflammatory and repair genes, and nearby amyloid deposits were nearly halved (Dec 2016 conference news). The antibody produced similar results in 5XFAD mice after 72 hours.
Injection of 50 mg/kg AL002a into 4-month-old 5XFAD mice for 14 weeks reportedly raised the number of CD11b-positive microglia by 50 percent. The number of microglia around amyloid plaques doubled, amyloid load cut in half. Treated mice performed like wild-type in the radial arm water maze and novel-object-recognition tasks (May 2019 conference news).
In November 2018, AL002 started INVOKE, a Phase 1 trial at six sites in the U.S., Australia, and the U.K. In its single-ascending-dose phase, 51 healthy adults receive infusions of one of nine escalating doses or placebo; in the multiple-ascending dose phase, 10 AD patients will receive drug, two placebo. Outcomes include safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. According to Alector, dosing started in May 2019; the trial is projected to finish in December 2019 (see press release).
For all trials of AL002, see clinicaltrials.gov.
Last Updated: 11 Jun 2019
- Inflammation Helps Microglia Clear Amyloid from AD Brains
- Antibodies Against Microglial Receptors TREM2 and CD33 Head to Trials
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