People with ALS are known to have increased inflammatory changes in the muscle control regions of the brain (motor cortices) as learned from  brain PET scan biomarkers and from postmortem studies. Clinical trials using smaller sample sizes and biomarker readouts are the need of the hour in early phase drug development in ALS.

MN-166 (ibudilast) is an oral experimental study medication known to inhibit microglial activation/neuroinflammation in preclinical studies. This early phase clinical trial evaluated the biological activity of MN-166 100mg/day on blood and brain PET imaging biomarkers in ALS. This biomarker-driven clinical trial was recently conducted at Massachusetts General Hospital, Boston, USA and South Shore Neurological Associates, NY, USA. In this open label trial, 35 eligible ALS participants underwent ibudilast treatment up to 100 mg/day for 36 weeks. Of these, 30 participants were enrolled in the main study cohort and were included in biomarker, safety and tolerability analyses. Five additional participants were enrolled in the expanded access arm, who did not meet imaging eligibility criteria and were included in the safety and tolerability analyses.

The study concludes that following treatment with MN-166 (ibudilast) in ALS participants, there were no (a) detectable biological impact of MN-166 up to 100mg/day dosages on lowering brain inflammation measured by PBR28-PET SUVR over 12–24 weeks (N=22 participants) or (b) lowering disease activity as measured by blood neurofilament light levels over 36–40 weeks (N=10 participants). Dose reductions and discontinuations due to treatment emergent adverse events were common at this dosage (100mg/day) in ALS participants.

Overall 100mg/day MN-166 was safe and showed no drug related serious adverse events. Several participants experienced GI related, fatigue and insomnia adverse events. Thirty seven percent of study participants could not tolerate 100 mg/day and underwent dose reduction to 60 to 80 mg/day and 31% participants discontinued study drug early due to drug related adverse events. This study was not designed to make conclusions on clinical efficacy. A new larger trial is currently underway in the USA and Canada by MediciNova to evaluate the optimal dose range for safety, tolerability and efficacy of MN-166 in patients with ALS.

This project was funded by an anonymous donor to the Mass General ALS research program and Ride for Life. Medicinova provided study drug, electronic database support, monitoring and partial funding support. We express our thanks and deep appreciation to all our ALS study participants and their families for their participation in the study.