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
AL003 is a monoclonal antibody being co-developed by Alector and Abbvie. According to Alector, it counteracts the function of Siglec-3, a microglial transmembrane receptor that reportedly interacts with TREM2 (Oct 2015 news). The gene encoding Siglec-3, CD33, has been associated with AD risk via a protective variant, expression levels, and alternative splicing (Estus et al., 2019; Katsumata et al., 2019; Bertram et al., 2008).
In March 2019, AL003 entered the clinic with a 54-person trial being run at 6 sites in the U.S and Melbourne, Australia (May 2019 conference news). In a single-ascending-dose phase, 42 healthy participants receive infusions of one of seven escalating doses; in a subsequent multiple-ascending-dose phase, 10 participants with AD will receive drug, two placebo. Outcomes include safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. The trial is projected to finish in May 2021.
For all trials of AL003, see clinicaltrials.gov.
Last Updated: 22 Dec 2020
- Antibodies Against Microglial Receptors TREM2 and CD33 Head to Trials
- Alzheimer’s Risk Genes Interact in Immune Cells
- Estus S, Shaw BC, Devanney N, Katsumata Y, Press EE, Fardo DW. Evaluation of CD33 as a genetic risk factor for Alzheimer's disease. Acta Neuropathol. 2019 Aug;138(2):187-199. Epub 2019 Apr 4 PubMed.
- Katsumata Y, Nelson PT, Estus S, Alzheimer's Disease Neuroimaging Initiative (ADNI), Fardo DW. Translating Alzheimer's disease-associated polymorphisms into functional candidates: a survey of IGAP genes and SNPs. Neurobiol Aging. 2019 Feb;74:135-146. Epub 2018 Oct 23 PubMed.
- Bertram L, Lange C, Mullin K, Parkinson M, Hsiao M, Hogan MF, Schjeide BM, Hooli B, Divito J, Ionita I, Jiang H, Laird N, Moscarillo T, Ohlsen KL, Elliott K, Wang X, Hu-Lince D, Ryder M, Murphy A, Wagner SL, Blacker D, Becker KD, Tanzi RE. Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE. Am J Hum Genet. 2008 Nov;83(5):623-32. PubMed.
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