Abstract
Oxidative/nitrosative stress and mitochondrial dysfunction is a hallmark of amyotrophic lateral sclerosis (ALS), an invariably fatal progressive neurodegenerative disease. Here, as an exploratory arm of a phase II clinical trial (EudraCT Number 2017-005065-47), we used high performance liquid chromatography(HPLC) to investigate changes in the metabolic profiles of serum from ALS patients treated weekly for 4 weeks with a repeated sub-cutaneous dose of 1 mg/kg of a proprietary low molecular weight dextran sulphate, called ILB®. A significant normalization of the serum levels of several key metabolites was observed over the treatment period, including N-acetylaspartate (NAA), oxypurines, biomarkers of oxidative/nitrosative stress and antioxidants. An improved serum metabolic profile was accompanied by significant amelioration of the patients’ clinical conditions, indicating a response to ILB® treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes.
Highlights
Introduction conditions of the Creative CommonsAmyotrophic lateral sclerosis (ALS, known as Lou Gehrig’s disease) is the most common type of motor neuron disease
The deranged neuronal function that is associated with the oxidative/nitrosative stress and mitochondrial dysfunction that characterizes the pathophysiological progress of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS) [3] is reflected by changes in related metabolites in blood
Samples were centrifuged at 20,690× g for 15 min at 4 ◦ C to remove precipitated proteins and the clarified supernatants stored at −80 ◦ C until the HPLC analysis of fat-soluble vitamins and antioxidants
Summary
Amyotrophic lateral sclerosis (ALS, known as Lou Gehrig’s disease) is the most common type of motor neuron disease. The deranged neuronal function that is associated with the oxidative/nitrosative stress and mitochondrial dysfunction that characterizes the pathophysiological progress of neurodegenerative conditions such as ALS [3] is reflected by changes in related metabolites in blood. When measured, these metabolites can be used as biomarkers of tissue function and, of disease progression and/or patient response to treatment [4]. The primary outcomes of this clinical trial are reported elsewhere [7]
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