Riluzole

Okamoto M, et al. evaluated the disease-modifying effects of riluzole, a glutamate modulator, in 5XFAD transgenic mice, a model of early-onset familial Alzheimer's disease characterized by amyloid β pathology. Chronic riluzole treatment administered from 1 to 6 months of age significantly enhanced cognitive performance and reduced levels of Aβ42, Aβ40, Aβ oligomers, and amyloid plaque load. RNA sequencing revealed that riluzole reversed many of the gene expression changes observed in the hippocampus, particularly in disease-associated microglia (DAM) markers, as well as in neuronal and astrocytic genes. Notably, riluzole normalized alterations in the expression of NMDA receptor subunits that are essential for learning and memory.

Fig. 1 Expression changes in cell-type-specific markers and hippocampal NMDA receptor subunits are reversed by riluzole treatment. (Okamoto M, et al., 2018)

Fehlings MG, et al. randomized 193 patients with acute cervical spinal cord injury to receive riluzole (100 mg twice daily for 24 hours, followed by 50 mg twice daily for 13 days) or placebo. The trial was halted prematurely due to the COVID-19 pandemic, enrolling 54.9% of the planned participants. The primary analysis did not show significant improvement in upper extremity motor scores with riluzole (mean gain, 1.76 points; 95% CI, –2.54 to 6.06). However, pre-planned subgroup analyses revealed significant functional gains across all injury severity categories (AIS A, B, and C).

Fig. 2 Consolidated Standards of Reporting Trials (CONSORT) flow diagram of the Riluzole in Spinal Cord Injury Study (RISCIS) at the 180-day follow-up visit. (Fehlings MG, et al, 2023)