The ALS genes found in genetic studies of the BCRM UMC Utrecht enable personalized medicine, i.e. testing medication for specific ALS patient groups. BCRM researchers showed that ALS patients with the UNC13A gene variant had a benefit from treatment with lithium, even though this medication lacks effects for ALS patients in general.

Incorporating genetic data in clinical trials

In a joint effort, Project Mine partners from the BCRM UMC Utrecht, King’s College London and Turin University, reanalyzed the data from 3 previously conducted clinical trials of Lithium in ALS. In this post-hoc analysis they incorporated genetic data to see whether genetic subgroups of patients responded differently to treatment.

Lithium for a specific subgroup of ALS patients

The study shows that patients with C9orf72 repeat expansions and those homozygous for a SNP in the UNC13a gene have a shorter survival, and that these effects on survival may also influence the outcome of a trial. Even more intriguing, there is a survival benefit for UNC13a positive patients on lithium compared to those on placebo (the 12-month survival probability increased from 40 to nearly 70%). This is in contrast to the overall meta-analysis including all patients regardless of genetics, which was negative. The next step will be to perform a new confirmatory trial including only UNC13a positive patients. Plans for a multicentre, European trial are underway. Project lead, Michael an Es: “This finding is a first step towards personalized medicine for ALS. With the results from project MinE, we are planning to re-analyze more clinical trials. The aim is to personalize ALS treatment.”

ALS genes in clinical trials

This study shows the importance of including genetic information in clinical trials for ALS. We need to standardize genotyping in order to optimize randomization and the analysis of future clinical trials. Patients with specific mutations in certain ALS-genes might need specific treatments.

UK researcher Ammar Al-Chalabi said: “These results show the importance of understanding the genetic makeup of people in a clinical trial”.


The scientific publication ‘Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials’ was published this week in the journal Neurology and is full-text available open acces.