Lithium carbonate as treatment in patients with amyotrophic lateral sclerosis carrying the UNC13A at risk genotype

Over the last 2 decades, more than 50 large randomize controlled trial in amyotrophic lateral sclerosis (ALS) were negative. One of the reasons for this lack of succes is the high degree of heterogeneity in ALS. Currenlty, all patients (with very different disease onset-progressionetiologies) are lumped together. In order to improve the quality of trial design, novel strategies to identify more homogeneous patient pools are urgently needed.
Several trials studying the effect of lithium carbonate in patients with ALS were also negative. However, a recent meta-analysis of the lithium trials in ALS reported that patients with an UNC13A risk allele (homozygous for the C-allele of rs12608932) did have a clear survival benefit. Such patients have a more aggressive form of the disease, but represent only 12 to 19% of the population in Europe. The aim of this study is to perform a randomized placebo-controlled trial to confirm the efficacy of lithium in patients with ALS carrying the UNC13A risk allele. As this is only a proportion of the ALS population, such a study can only be performed in a multicenter study.