A Novel TREM2 Small Molecule Agonist MTX46943 Re‐Programs Human Microglia and Reduces Amyloid Pathology <i>In Vivo</i>
Muna Therapeutics is advancing MTX46943, a selective, potent, safe and brain exposed small molecule TREM2 agonist into clinical studies for the treatment of early AD. We demonstrate here key differentiated aspects of the mechanism by which MTX46943 targets TREM2 and induces microglial re-programming via receptor complex formation and stabilization. Chronic treatment of MTX46943 robustly and significantly reduces brain amyloid pathology at doses shown to promote peripheral and central biomarker responses. The present studies collectively support the best-in-class therapeutic potential of MTX46943 for the treatment of Alzheimer´s disease.
Authors
- Ivana Geric (ORCID: https://orcid.org/0000-0002-6184-0594)
- Niels Plath (ORCID: https://orcid.org/0000-0002-2965-3027)
- Ashley L. Comer (ORCID: https://orcid.org/0000-0002-7073-892X)
- Arya Lekshmi Nair (ORCID: https://orcid.org/0000-0002-8981-4283)
- Peter Flagstad
- Ninna Ahlmann Frederiksen
- Maria Dalby (ORCID: https://orcid.org/0000-0001-6018-3468)
- Joachim Vilstrup (ORCID: https://orcid.org/0000-0002-7941-1536)
- Rita J. Balice‐Gordon (ORCID: https://orcid.org/0000-0002-9950-7965)
- Ashley Lu
- Laura Sans
- Jin Zheng
- Tina Sommer Bisgaard
- Manuela Polydoro
- Morten S Andersen
- Leen Wolfs
Institutions
- Q Therapeutics (United States) (US)
- MC2 Therapeutics (Denmark) (DK)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz70859_100777
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00