UM contributes to landmark study uncovering new genetic causes of ALS

UM has contributed to a landmark international study published in the scientific journal Nature Genetics, which significantly advances our understanding of the genetic basis of amyotrophic lateral sclerosis (ALS).

The study, conducted as part of the global Project MinE initiative and led by University Medical Center Utrecht in collaboration with several international partners, analysed genetic data from thousands of individuals with ALS, including samples from Malta’s national ALS DNA Bank.

The findings reveal that a genetic cause can now be identified in approximately one in four people living with ALS, an increase from previous estimates of one in five.

Researchers also identified several previously unknown genetic alterations associated with the disease. These discoveries expand the number of genes linked to ALS and provide new insights into its underlying biological mechanisms.

ALS is a progressive neurodegenerative condition that affects motor neurons, the nerve cells controlling movement, leading to muscle weakness, paralysis, and ultimately death, typically within a few years of diagnosis.

Malta has one of the highest incidence rates of ALS in Europe. While more than one in ten people with ALS have a family history of the disease in Malta, the majority of cases occur sporadically, with both genetic and environmental factors contributing to disease development.

The study highlights that ALS is often not caused by just one faulty gene. Instead, it can result from a combination of several small genetic changes that together increase a person’s risk of developing the disease.

“This study marks an important step forward in uncovering the genetic complexity of ALS,” explained Professor Ruben J. Cauchi who leads the Motor Neuron Disease Laboratory at the University of Malta. “Such insights are essential if we are to develop targeted therapies that can make a real difference to patients.”

Participation by researchers from the University of Malta contributes to ongoing efforts to understand how genetic variation influences ALS across different populations. Previous research involving Maltese ALS patients has already indicated distinct genetic patterns, underlining the importance of including diverse populations in global studies.

“Our continued participation in international efforts such as Project MinE ensures that Malta contributes meaningfully to this global endeavour,” Professor Cauchi noted. “Crucially, our involvement ensures that these discoveries are also relevant to Maltese ALS patients.”

This collaborative effort demonstrates the value of international research partnerships in tackling complex diseases and reinforces the University of Malta’s commitment to contributing to cutting-edge biomedical research with global impact.

The University of Malta’s participation in Project MinE is supported by the Xjenza Malta Research Excellence Programme, Rotary Club La Valette, and the Anthony Rizzo Memorial ALS Research Fund, with the latter two facilitated by the University of Malta’s Research, Innovation and Development Trust (RIDT).

Publication

Hop et al. Large-scale exome analyses reveal new rare variant contributions in amyotrophic lateral sclerosis. Nat Genet (2026). https://doi.org/10.1038/s41588-026-02535-9