Oxidative Stress Biomarkers in ALS: Impact of Antioxidant Treatment and Future Drug Research Implications

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurological disease leading to death within on average three years. ALS can occur at any adult age and is highly variable in its clinical presentation. This complicates the diagnosis of ALS, leading to a diagnostic delay of 12-15 months and a misdiagnosis rate of 10%. Together with Treeway B.V., the UMCU will assess new biomarker-based diagnostics to timely initiate multidisciplinary care and improve quality of life.

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease for which the diagnosis is very difficult. Patients may have to wait one to two years for a final diagnosis. There are no effective treatments available and median survival is a mere 18 months after diagnosis. One possible cause of ALS is increased metabolism leading to ‘oxygen damage’ or 'oxidative stress.' In this project, we measured two proteins in the blood that indicate the amount of oxygen damage, namely: 8-OHdG and malondialdehyde.

In the first part of the project, we developed a method to measure these proteins in collaboration with Treeway B.V. and the University of Queensland. In the second part, we analyzed blood samples from patients participating in a drug trial. 21 people with ALS were given an antioxidant for 12 weeks. Both proteins showed a clear decrease in the blood during the treatment and increased again after the cessation of treatment. This is a crucial indication that the proteins we are measuring are indeed related to oxidative stress.

These results hold important value, not only to potentially improve the diagnosis of ALS, but also as marker of potential treatment response. Especially the latter could have important scientific and societal impact by speeding up drug development and finding effective therapy for this dibilitating disease.

Together with Treeway B.V., we are now engaged in a larger drug study with an antioxidant to further validate these biomarkers for drug research in ALS. The COVID pandemic has distrupted the original planned analysis of a larger cohort of blood samples to evaluate the diagnostic utility of these markers. Final project results and publications are expected in 2025.