Maltese at higher risk of developing ALS, may be due to genetic insularity

Maltese people are at higher risk of developing ALS, and the cause may be the genetic insularity of the islanders, according to a landmark study from the University of Malta.

This could change in the coming centuries as the number of Maltese in mixed relationships grows and the gene pool becomes more diversified, after millennia of being isolated from mainland Europe.

The findings of the five-year study will be published in the neurobiology of aging diary.

ALS is a disease that destroys the nerves that interact with the muscles in the body, typically leading to complete paralysis of the body, depriving patients of their ability to walk, talk, eat, and breathe.

In Malta, around one patient is diagnosed with ALS each month, and around 15 people are known to have the disease at any given time. Some patients die months after diagnosis, while others survive for years.

Over the past five years, 50 ALS patients have participated in this research, an impressive number considering Malta’s small population, according to Prof. Ruben J Cauchi, director of the university. Laboratory of Motor Neuron Diseases.

Maltese men were found to be more likely than women to develop ALS, with symptoms developing most frequently between the ages of 45 and 75. In rare cases, the disease was found to strike at a younger age, with one extremely rare case found at 18 months. The boy was found to have what is known as the juvenile ALS gene. The cause of ALS in half of Malta’s patients can be traced back to genetics.

For this research, the genes of Maltese ALS patients were compared with those of healthy volunteers. Most of the patients came from areas of high population density, including the center and southeast of the island. A higher than expected number of cases was identified in Gozo, Cauchi said.

“The results are exciting because they not only point to important epidemiological issues, but also expose the unique genetic landscape of ALS in Malta.

“The percentage of ALS cases with a genetic explanation in Malta is one of the highest in the world, and only comparable to that of Sardinia. One possible culprit is our genetic insularity shaped by millennia of relative isolation from mainland Europe.”

This could change in the coming centuries as more Maltese have relationships with other ethnicities, he added.

How will the research help future patients?

There is no cure for ALS; however, efforts to find a treatment that can delay progression have intensified internationally in recent years. For more than a decade, Cauchi and her team have investigated the genetics and mutations that significantly contribute to the development of ALS.

This latest discovery could speed diagnosis and identify patients eligible for experimental treatments.

Assessing a person’s selected set of genes could be done in a day, Cauchi explained, as his lab has identified the unique set of genes and DNA changes in Maltese ALS patients.

“The five genes that top the list as the most frequently damaged in Maltese ALS patients, they are a rare cause of ALS in Europeans. This confirms previous research that treatment that targets the genes of ALS patients may not be effective in Maltese,” he said.

Right now, the research team is looking at these high-ranking genes in more detail.

The findings will also allow professionals to provide genetic counseling to parents-to-be who are carriers of genes that could see the development of ALS in their children.

Study co-authors include Maia Farrugia Wismayer, Rebecca Borg, Karl Bonavia, Andrew Farrugia Wismayer and Neville Vassallo from the University of Malta; Malcolm Vella, Charmaine Chircop, Josanne Aquilina and Doriette Soler from Mater Dei Hospital; and Adrian Pace of Karin Grech and Gozo General Hospitals.

Research at the Motor Neurone Disease Laboratory is currently funded by the Malta Science and Technology Council Research Excellence Program and Internationalization Partnership Award, the Anthony Rizzo Memorial ALS Research Fund facilitated by the University of Malta Research Trust, and an Endeavor Scholarship (part-funded by the European Social Fund).

Those who require more information about the research or are interested in sponsoring research can contact mnd.research@um.edu.mt