 A new clinical trial suggests levosemendin could improve respiratory function in patients with amiotrophic lateral sclerosis. ALS is an adult onset neurodegenerative disease that results in progressive weakness. Those affected by the disease typically die within three to four years of diagnosis due to respiratory failure commonly resulting from weakening of the diaphragm. Prior studies indicate that levosemendin, a calcium sensitizer on the market since 2000 for the treatment of acute worsening of severe heart failure, can also boost the force and efficiency with which the diaphragm contracts. This prompted researchers to investigate whether levosemendin is clinically beneficial to those with ALS. The Phase 2 trial used a randomized, double-blind, placebo-controlled crossover design to evaluate the efficacy and safety of oral levosemendin in 66 patients with ALS. The patients received three 14-day periods of treatment in random order, twice daily dosing with one milligram levosemendin, one milligram levosemendin taken in the morning followed by a placebo in the evening, or twice daily dosing of placebo. Open label follow-up was offered starting with one milligram levosemendin in the morning for two weeks followed by an increase to one milligram twice daily if tolerated. The primary endpoint was slow vital capacity in the sitting position. Although this endpoint was not met, post-hoc analysis indicated significant and dose-dependent treatment effects between levosemendin and placebo in supine slow vital capacity after a 14-day treatment period. This observation has important implications as diaphragmatic performance is more dramatically reduced by lying versus sitting and the first clinical signs of respiratory insufficiency in ALS often appear during sleeping or when lying down. It's possible that upright vital capacity might not reveal abnormalities that are noticeable in the supine position. Headache and increased heart rate were more common with levosemendin than placebo and showed a dose-dependent increase in frequency. Although most patients tolerated levosemendin well and no significant differences between the treatments were observed for other adverse events. The trial provides the first clinical evidence that levosemendin may improve respiratory function in patients with ALS. While encouraging, larger and longer studies are needed to confirm the results.