New publication in the Journal of Cardiovascular Pharmacology: Working hypothesis for mechanisms of action of levosimendan in patients with ALS

A Review article summarizing the Potential of Levosimendan in the Management of ALS: Overview of a Working Hypothesis

Intravenous Levosimendan is an inodilator that has been used to treat acute heart failure since 2000 and is approved in nearly 60 countries worldwide. Levosimendan was discovered in Orion in 1990’s. Recently, the effects of levosimendan on skeletal muscle suggested a possible clinical value of levosimendan in treating patients with amyotrophic lateral sclerosis (ALS) and Orion launched a clinical delevopment program to study the effects of oral levosimendan on respiratory function in patients with ALS. The results of Phase 2 clinical trial (LEVALS) were promising: in 66 patients, supine (but not sitting) slow vital capacity (SVC) measuring respiratory function was significantly higher after 14 days treatment on oral levosimendan (1 and 2 mg) compared to placebo. The clinical effects of oral levosimendan are being confirmed in the ongoing REFALS phase 3 trial (NCT03505021) in patients with ALS.

In addition to the inotropic effect, a number of other well-documented effects, including vasodilation and organ protection, have been reported with levosimendan. This review article published in the Journal of Cardiovascular Pharmacology, considered the various known actions of levosimendan for their relevance to patients with ALS. “Levosimendan may have an effect on breathing muscles in ALS, and potentially has other effects too, raising the possibility that it could relieve some symptoms for people with ALS.  There are currently no effective treatments for this devastating disease and there is an urgent need for novel therapies.” said Prof. Ammar Al-Chalabi, the first author of the review publication.

 

 

Mechanisms of action of levosimendan hypothesized to be relevant to its use in ALS.

 

17 October, 2019