Pharmacodynamic biomarkers responsive to mutant huntingtin lowering in a Huntington's disease mouse model
• Candidate PET imaging biomarkers Pde10a, mHTT and D 1 R are responsive to early m Htt lowering. • Candidate CSF biomarkers Snc4b and Ace are responsive to early m Htt lowering. • Early intervention with moderate (∼50 %) whole-body m Htt lowering is required to delay progression of phenotypes; late intervention resulted in minimal benefits.
Authors
- Jim Rosinski
- Longbin Liu (ORCID: https://orcid.org/0000-0003-3995-0196)
- Alan Miranda (ORCID: https://orcid.org/0000-0002-5381-015X)
- Joachim Fentz (ORCID: https://orcid.org/0000-0002-9334-1298)
- Marleen Verhoye (ORCID: https://orcid.org/0000-0002-6267-0611)
- Jeroen Verhaeghe (ORCID: https://orcid.org/0000-0002-4493-1902)
- Liesbeth Everix (ORCID: https://orcid.org/0000-0001-5985-1609)
- Ignacio Muñoz-Sanjuán (ORCID: https://orcid.org/0000-0003-0353-3577)
- Tim Fieblinger (ORCID: https://orcid.org/0000-0002-9348-3595)
- Jonathan Bard (ORCID: https://orcid.org/0000-0002-5097-1361)
- Jannis Gundelach
- Daniele Bertoglio (ORCID: https://orcid.org/0000-0003-4205-5432)
- Mari J. Aaltonen (ORCID: https://orcid.org/0000-0002-7333-9334)
- John C. Obenauer (ORCID: https://orcid.org/0000-0002-7962-8890)
- Franziska Zajicek (ORCID: https://orcid.org/0000-0001-5410-687X)
- Thomas Wild (ORCID: https://orcid.org/0000-0002-2455-3625)
- Deanna M. Marchionini (ORCID: https://orcid.org/0000-0003-2071-1064)
- Stef De Lombaerde (ORCID: https://orcid.org/0000-0002-5307-3575)
- Steven Staelens (ORCID: https://orcid.org/0000-0003-3376-0519)
- Jonathan Greene
- Joëlle van Rijswijk (ORCID: https://orcid.org/0000-0001-6971-7358)
- Carleen M Kluger
- Aglaia Kakoulidou
Institutions
- University of Antwerp (BE)
- CHDI Foundation (US)
- Rancho BioSciences (United States) (US)
- Evotec (United States) (US)
Publication Details
- Journal
- Neurobiology of Disease
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1016/j.nbd.2025.106906
- Citations
- 3
- Primary Topic
- Genetic Neurodegenerative Diseases
- Type
- article
- Field-Weighted Citation Impact
- 2.73
Funders
- CHDI Foundation