Abstract
Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease that involves progressive loss of voluntary muscle and ultimately, respiratory function, which is the primary cause of death in ALS patients. Respiratory vital capacity (VC) measurements are objective, reproducible, and directly related to survival. Respiratory function is known to be negatively affected in individuals with excess abdominal fat contributing to a chronic innate immune inflammatory state. To test whether ALS patients might have a body mass index (BMI) related VC response to the innate immune system regulator NP001, clinical results from two NP001 phase 2 trials were evaluated in an intent-to-treat manner, stratified by BMI measurements. Slowing of progressive VC loss and extension of overall survival (OS) occurred primarily in ALS patients who were overweight with a BMI ≥ 25 (70% of patients in the phase 2 trials). Innate immune dysfunction is a characteristic of ALS patients ≤ 65 years of age, and in this group both VC and OS changes in response to NP001 were most significant. This study represents a novel approach to ALS, wherein VC and OS were both significantly improved through immunologic, not neurologic modulation with NP001, a precursor to the dominant regulator of inflammation, taurine chloramine.