NEW research has shown that tetramethylpyrazine nitrone is safe for patients with amyotrophic lateral sclerosis (ALS), and may slow the decline in grip strength, particularly in younger patients with slower disease progression, though it does not significantly impact overall functional outcomes.
This phase 2, double-masked, placebo-controlled clinical trial evaluated the safety and efficacy of tetramethylpyrazine nitrone in ALS patients. Conducted across 11 centres in China from December 2020 to July 2023, the study enrolled 155 participants aged 45 to 70 years with disease onset within two years. Eligible patients had an ALS Functional Rating Scale–Revised (ALSFRS-R) score of at least 2 on each item and a forced vital capacity (FVC) of at least 80%. Participants were randomly assigned to receive either a low dose (600 mg twice daily), a high dose (1200 mg twice daily), or a placebo for 180 days. The primary outcome was the change in ALSFRS-R score, while secondary outcomes included FVC, grip strength, and quality-of-life measures.
No significant differences were found in the primary ALSFRS-R score changes between the treatment groups and placebo. The least squares mean difference was -0.89 points (95% CI, -3.25 to 1.48) for the low-dose group and -0.20 points (95% CI, -2.48 to 2.07) for the high-dose group. However, high-dose tetramethylpyrazine nitrone significantly slowed the decline in grip strength at 180 days, with a least squares mean difference of 2.46 kg (95% CI, 0.15-4.76 kg). This effect was more pronounced in patients under 65 with a slower disease progression, showing an improvement of 3.63 kg (95% CI, 0.84-6.41 kg). Additionally, these patients exhibited better bulbar and respiratory function scores. Adverse events were generally mild to moderate across all groups, with no severe treatment-related complications or deaths.
The results indicate that tetramethylpyrazine nitrone is well-tolerated and may provide clinical benefits in specific subgroups of ALS patients, particularly those who are younger with a slower disease trajectory. While the treatment did not improve overall ALSFRS-R scores, its effect on grip strength suggests potential utility in maintaining motor function. Future studies should focus on longer treatment durations, larger sample sizes, and identifying patient subgroups most likely to benefit. These findings contribute to the evolving landscape of ALS management, highlighting the need for targeted therapeutic strategies in clinical practice.
Katrina Thornber, EMJ
Reference
Liu X et al. Tetramethylpyrazine nitrone in amyotrophic lateral sclerosis: a randomized clinical trial. JAMA Netw Open. 2025;8(2):e2461055.
