For the first time, a variant in UBQLN4 gene has been associated with amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig’s disease) – a progressive disease resulting in the loss of nerve cells that control muscle movement, which eventually leads to paralysis and death. The study, published in the journal eLife, also describes how this gene variant disrupts a cellular process that drives motor neuron development. This new insight opens the door to potential treatment targets for ALS.

The earlier discovery of mutations in UBQLN2 gene, which causes ALS and ALS/dementia, led to the screening of the UBQLN family of genes in a large cohort of patients with familial ALS, resulting in the identification of the UBQLN4 mutation.

Using a zebrafish model, researchers were able to reverse the defects caused by the UBQLN4 gene variant by inhibiting the beta catenin signaling pathway with the drug quercetin. These findings suggest that this pathway could be targeted for treatment. More research will be needed before a similar drug could be shown to work in people with ALS.

The researchers say that, at present, they don’t know how common the UBQLN4 gene variant is among people with ALS, so making this determination will be an important focus for future research.

Paper: “A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis”
Reprinted from materials provided by the Ann & Robert H. Lurie Children’s Hospital of Chicago.

7 Ιουλίου, 2017