RT Journal Article
T1 Assessment of the therapeutic effect ofigs2.7, a ck1δ protein kinase inhibitor, in combination with riluzole for the treatment of als-associated tdp-43 proteinopathy
A1 Gómez Almería, Marta
A1 Martinez Gonzalez, Loreto
A1 Matos, Ana Teresa
A1 Rodríguez Cueto, Carmen Aurora
A1 Vaz, Ana Rita
A1 Martín Baquero, Raquel
A1 Pérez de la Lastra, Carmen
A1 Infantes, Rafael
A1 Fernández Ruiz, José Javier
A1 Palomo, Valle
A1 Gil, Carmen
A1 Brites, Dora
A1 Martinez, Ana
A1 Lago Femia, Eva De
AB Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease for which no effective treatments currently exist. The FDA and EMA have approved only riluzole, a drug that modestly extends patient survival by 3-18 months. In our research, we have identified a novel CK1δ inhibitor, IGS2.7, which modulates TDP-43 proteinopathy, the main ALS pathological hallmark, in both patient-derived cellular models and TgTDP-43 mice. To assess the potential of IGS2.7 as a therapeutic candidate and considering riluzole remains the standard care for ALS patients, we evaluated its effects in combination with riluzole. Our results demonstrate that co-administration of IGS2.7 and riluzole at effective doses does not cause adverse effects. However, no additional therapeutic benefit was observed beyond that of IGS2.7 monotherapy, suggesting that IGS2.7 may be viable as either a stand-alone treatment or as an adjunct to riluzole. Notably, when suboptimal doses of both drugs were administered, a combined effect was observed. This suggests that, once IGS2.7 reaches clinical testing, its use together with lower doses of riluzole may enhance therapeutic efficacy while potentially minimizing side effects. Additional in vivo pre-clinical studies will be required to further evaluate this possibility, although only clinical trials will ultimately determine its clinical relevance.
PB Elsevier
SN 0028-3908
YR 2025
FD 2025-12-11
LK https://hdl.handle.net/20.500.14352/131162
UL https://hdl.handle.net/20.500.14352/131162
LA eng
NO Gomez-Almeria M, Martinez-Gonzalez L, Matos AT, Rodriguez-Cueto C, Vaz AR, Martín-Baquero R, Pérez de la Lastra C, Infantes R, Fernández-Ruiz J, Palomo V, Gil C, Brites D, Martinez A, de Lago E. Assessment of the therapeutic effect of IGS2.7, a CK1δ protein kinase inhibitor, in combination with riluzole for the treatment of ALS-associated TDP-43 proteinopathy. Neuropharmacology. 2026 Mar 1;285:110804. doi: 10.1016/j.neuropharm.2025.110804. Epub 2025 Dec 11. PMID: 41389988.
NO 2025 Acuerdos transformativos CRUE
NO La Caixa and Luzón Foundations
NO Instituto de Salud Carlos III
NO Ministerio de Ciencia, Innovación y Universidades (España)
DS Docta Complutense
RD 21 mar 2026