First steps towards personalized medicineA study of ALS genes has shown the potential for treatment tailored to specific patient groups.

Genetics and clinical trials

A joint effort by Project MinE partners from the UMC Utrecht, King’s College London and Turin University, studied the influence of gene variations on the results of clinical trials of lithium, a treatment previously tested in ALS in the three countries.

Lithium for a specific subgroup of ALS patients

The researchers investigated two gene variations known to affect survival in ALS, C9orf72 expansion, and a variant in the UNC13A gene. The gene variations have been previously shown to worsen survival, but are not routinely tested for in clinical trials. The researchers wanted to see if a hidden effect of these variants had affected the trial results. They confirmed that people carrying the gene variants had a worse survival, and that they could affect the outcome of a trial. UK researcher Ammar Al-Chalabi said, “These results show the importance of understanding the genetic makeup of people in a clinical trial”.

Intriguingly, the researchers showed that people with the UNC13A gene variant had a benefit from lithium, even though this was not apparent in the study overall. The chance of surviving 12 months for people carrying the gene variant improved from 40% to nearly 70%. Because this test was not planned in the original trial design, it is important to confirm it in a new study. Project lead, Michael van Es said, “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.” Plans for a multi-centre, European trial of lithium in people with the UNC13A gene variant are underway.

ALS genes in clinical trials

This study shows the importance of including genetic information in clinical trials for ALS, and means it is important that the tests are done in a standard way in all centres. People with ALS who have mutations in certain genes might need specific treatments.


The scientific paper ‘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.

The MND Association posted a blog about the paper on the MND research blog.