We are very grateful for the continued support from the Dutch CampagneTeam Huntington foundation (CTH), which has just announced that they will fund our new project grant on Huntington’s disease (HD). This is a project together with our longstanding collaborator Prof Amalia Dolga (at the GRIP institute of the University of Groningen). It is an extension of an earlier project that the CTH funded, and which paid for the PhD research project of Dr. Greeshma Jain. She published several papers from her research on the structures and toxic properties of HD-related protein aggregates and how they are modulated by aggregation inhibitors [e.g. refs 1-4]. The new project will dive more deeply into these questions, with the aim of not only providing new insights into the mechanisms behind HD but also hopefully paving the way for new treatment strategies for HD.
We are extremely grateful to the foundation and especially also the many volunteers who made these funds possible. The support from foundations like the CTH has been critical for our past research into HD, especially during the recent years as the group moved from the US to the Netherlands. It is rewarding and important to see that the CTH recognizes the value of fundamental research – as it will be crucial for our future ability to target and treat this disease. The ideas and data behind this proposal are enabled by the hard work and great accomplishments of current and prior research team members working on our HD research, as well as our great collaborators in the Dolga group. In the Van der Wel lab, I note particular contributions from PhD students Dr Greeshma Jain and Raffaella Parlato, postdoc Dr Irina Matlahov, as well as multiple MSc students who contributed to our HD research projects over the years.
With the CTH funds, we look forward to pursuing further research into HD mechanisms, and how they can be disrupted, modulated or prevented. Keep posted for the outcomes enabled by this new funding!
Publications from our prior CTH project:
- Jain, G.; Trombetta-Lima, M.; Matlahov, I.; Ribas, H. T.; Chen, T.; Parlato, R.; Portale, G.; Dolga, A. M.; Van Der Wel, P. C. A. Inhibitor-Based Modulation of Huntingtin Aggregation Mechanisms Mitigates Fibril-Induced Cellular Stress. Nat Commun 2025, 16 (1), 3588. https://doi.org/10.1038/s41467-025-58691-9.
- Bagherpoor Helabad, M.; Matlahov, I.; Kumar, R.; Daldrop, J. O.; Jain, G.; Weingarth, M.; Van Der Wel, P. C. A.; Miettinen, M. S. Integrative Determination of Atomic Structure of Mutant Huntingtin Exon 1 Fibrils Implicated in Huntington Disease. Nat Commun 2024, 15 (1), 10793. https://doi.org/10.1038/s41467-024-55062-8.
- Parlato, R.; Jain, G.; Lasorsa, A.; Van Der Wel, P. C. A. Probing How Anti-Huntingtin Antibodies Bind the Fibrillar Fuzzy Coat Using Solid-State NMR. bioRxiv April 27, 2025. https://doi.org/10.1101/2025.04.25.650083.
- Van Ewijk, C.; Jain, G.; Knelissen, Y. K.; Maity, S.; Van Der Wel, P. C. A.; Roos, W. H. Direct Observation of Secondary Nucleation in Huntingtin Amyloid Formation by High-Speed Atomic Force Microscopy. J. Am. Chem. Soc. 2025, 147 (25), 21973–21984. https://doi.org/10.1021/jacs.5c05571.