The Maltese are at a greater risk of developing ALS and the cause may be the islanders’ genetic insularity, according to a landmark study by the University of Malta.
This could change over the coming centuries as the number of Maltese in mixed relationships grows and the gene pool becomes more diversified, following millennia of being isolated from mainland Europe.
The conclusions of the five-year study are set to be published in the Neurobiology of Aging journal.
ALS is a disease that destroys nerves that interact with the body’s muscles and typically leads to complete paralysis of the body, robbing patients of their ability to walk, speak, eat and breathe.
In Malta, around one patient is diagnosed with ALS every month, and some 15 people are known to have the disease at any one point in time. Some patients die months after diagnosis while others survive for years.
Over the past five years, 50 ALS patients participated in this research – an impressive number considering Malta’s small population, according to Prof. Ruben J Cauchi, the head of the university’s Motor Neuron Disease Laboratory.
Maltese men were found to be more likely than women to develop ALS, with symptoms most commonly developing between 45 and 75 years. In rare instances, the disease was found to strike at an earlier age, with an extremely rare case encountered at 18 months. The child was found to have what is known as the juvenile ALS gene. The cause of ALS in half of Malta’s patients is traced to genetics.
For this research, genes of Maltese ALS patients were compared to that of healthy volunteers. Most of the patients hailed from high population-density areas, including the centre and southeast of the island. A higher-than-expected number of cases was identified in Gozo, Cauchi noted.
“The results are exciting in that they not only flag important epidemiological aspects, but also expose the unique genetic landscape of ALS in Malta.
“The percentage of genetically-explained ALS cases in Malta is one of the highest in the world, and only comparable to that of Sardinia. A possible culprit is our genetic insularity shaped by millennia of relative isolation from mainland Europe.”
This might change over the coming centuries as more Maltese are having relationships with other ethnicities, he added.
How will the research help future patients?
There is no cure for ALS; however, efforts at finding treatment that could slow the progression have intensified internationally over the past few years. For over a decade, Cauchi and his team have been looking into the genetics and mutations that contribute significantly to the development of ALS.
This most recent discovery could quicken diagnosis and identify patients eligible for experimental treatments.
Screening of a person’s select gene set could be done in one day, Cauchi explained, as his lab has identified the unique set of genes and DNA changes of Maltese ALS patients.
“The five genes that top the list as the most frequently damaged in Maltese ALS patients are a rare cause of ALS in Europeans. This confirms previous research that treatment that targets the genes of patients with ALS may not be effective on Maltese people,” he said.
Right now, the research team is looking at these top-ranking genes in more detail.
The findings will also allow professionals to provide genetic counselling to prospective parents 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 from Karin Grech and Gozo General Hospitals.
Research at the Motor Neuron Disease Laboratory is currently funded by the Malta Council for Science and Technology Research Excellence Programme and the Internationalisation Partnership Award, the Anthony Rizzo Memorial ALS Research Fund facilitated by the University of Malta’s Research Trust, and an Endeavour Scholarship (part-financed by the European Social Fund).
Those who require more information about the research or are interested in sponsoring research can get in touch on mnd.research@um.edu.mt