University of Malta researchers have revealed how disruption of the DCTN1 gene causes amyotrophic lateral sclerosis (ALS). The new study published in the scientific journal Frontiers in Neuroscience has implications on the development of treatments for this relentless disease.

ALS is a neurological disease attacking the nerve cells or neurons that control the muscles of the body. Due to the disease, muscles stop functioning leading to difficulties with walking, talking, eating, and, eventually breathing. Only one drug is available for ALS patients and it is widely known to be ineffective at halting disease progression.

Previous research has determined that the genes that cause ALS in Malta are different than those reported in other European populations. DCTN1 is one of the genes that is relatively much more damaged in Maltese ALS patients compared to their European counterparts.

In the pioneering study, researchers inactivated the DCTN1 gene in fruit flies to discover that this triggered symptoms that overlap those observed in ALS patients having faults in the same gene. Flies developed reduced mobility and a deterioration of the contact points between neurons and muscles. Flies have long been used by scientists because of the remarkable genetic and biological similarities to humans.

The scientists then studied how neurons without DCTN1 differed from healthy neurons. They found that several genes with a critical function in neurons were incorrectly edited.

“It is remarkable that some of the genes that we identified are well known to be incorrectly edited in postmortem brain samples of ALS patients,” explained the head of the Motor Neuron Disease Laboratory at the University of Malta, Prof. Ruben J. Cauchi.

“Besides confirming the relevance of our discoveries to the real-world disease process, we have shown that no matter what the cause of ALS, the disease mechanism appears to remain constant,” added Prof. Cauchi.

The researchers are confident that this new information will strengthen their resolve to design new ALS therapies that correct the wrong editing in crucial neuronal genes. This is expected to not only reverse the most problematic consequences in ALS patients in which DCTN1 is damaged but also in a broad spectrum of patients.

Study co-authors are Dr Rebecca Borg, Dr. Paul Herrera, Angie Purkiss, and Rebecca Cacciottolo.

Research at the Motor Neuron Disease Laboratory at the University of Malta is presently funded by the Malta Council for Science & Technology Research Excellence Programme, a Tertiary Education Scholarship, and the Anthony Rizzo Memorial ALS Research Fund facilitated by the University of Malta’s Research Trust (RIDT).