Safety and tolerability of Trimetazidine in amyotrophic lateral sclerosis (ALS)

Currently, there is a high unmet medical need for patients with ALS and effective treatment modalities are desperately needed. About half of all patients with ALS experience a change in their energy use that causes their body to consume more energy, which accelerates the spreading of ALS throughout the body. We showed previously that this change in energy use, called hypermetabolism, is clinically important as it is linked to an increased risk of death and faster rate of progression in people with ALS. In this project, we aim to reduce hypermetabolism in patients with ALS and counter its detrimental consequences. Trimetazidine, a partial fatty acid oxidation inhibitor, has been shown to reduce hypermetabolism in patients with chronic heart failure and is licensed as treatment for angina. Trimetazidine has a favourable safety profile and, more importantly, reduces the expression of oxidative stress markers that are also increased in patients with ALS. With growing evidence linking oxidative stress, metabolism and ALS, Trimetazidine may lower the occurrence of hypermetabolism and, potentially, slow disease progression in patients. The aim of this study is to verify target-engagement, and to study a unique composition of proteins/compounds in the blood that can be used as markers of disease progression. We will study the safety and tolerability of Trimetazidine in patients with ALS. This study will provide significant insight into the biological response when targeting metabolic parameters in patients with ALS. In addition, this trial will set up an international infrastructure to evaluate potential targets for ALS and mediate the adoption of early-stage clinical studies to drive pivotal future rials.