Treatment that targets the genes of patients with ALS may not be effective on Maltese people, University of Malta researchers have found.

The researchers, together with international peers, have just unlocked long-hidden secrets in the DNA of Maltese patients with amyotrophic lateral sclerosis (ALS). Results will soon be published in the European Journal of Human Genetics.

ALS is a progressive neurological disease that destroys nerves that interact with the body’s muscles. The disease typically leads to complete paralysis of the body, robbing patients of their ability to walk, speak, eat and breathe.

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, senior lecturer Ruben Cauchi and his team have been looking into the genetics and mutations that contribute significantly to the development of ALS.

In 2017 the University of Malta set up a national ALS registry and biobank to collect data on patients’ residence, occupation, lifestyle, environmental exposures and blood samples.

So far, data has been collected on about 38 ALS patients and 50 ‘healthy’ people for comparison.

In Malta, there are usually some 11 new ALS patients every year, and some 15 with the disease at any one point in time. Some patients die months after diagnosis while others survive for years.

In the first study based on information recorded at the biobank, University of Malta researchers discovered ‘unique’ flaws in genes linked to ALS.

“The DNA results caught us by surprise. The most frequently mutated ALS genes around the globe were flawless in Maltese patients,” lead researcher Cauchi said.

We are working towards personalised medicine so that patients can receive therapy that actually works for them

Collaborating with scientists at the University Medical Centre, in Utrecht, The Netherlands, the local researchers found that ALS patients in Malta did not have flaws in the four genes that are known to contribute to a major number of ALS cases worldwide.

However, the results also show that, unlike other countries, the cause of ALS in half of Malta’s patients could be traced to genetics.

 “We established that genetic factors play a significant role in causing ALS in Malta. Our results underscore the unique genetics of the Maltese population, shaped by centuries of relative isolation. Inbreeding and lack of a diverse gene pool could all be contributing factors.”

These differences ultimately mean that the gene-targeted treatment that is being developed for people with ALS abroad will not work on Maltese patients.

“This treatment would, of course, target those four most frequently mutated ALS genes and would not work in Malta. This means that Malta needs to carry out its own research,” Cauchi said.

“The ultimate aim of all the research carried out about ALS is to be able to treat patients. We are working towards personalised medicine so that patients can receive therapy that actually works for them,” said study co-author Maia Farrugia Wismayer.

She is meanwhile looking into the possible environmental causes of ALS in Malta.

Study co-authors included Rebecca Borg, Karl Bonavia, Andrew Farrugia Wismayer and Neville Vassallo from the University of Malta, Malcolm Vella from Mater Dei Hospital and Joke JFA van Vugt, Brendan J Kenna, Kevin P Kenna, and Jan H Veldink from UMC Utrecht.

The study was funded by the University of Malta Research Excellence Fund, an Endeavour Scholarship (part-financed by the European Social Fund), an EMBO fellowship, a Malta Council for Science and Technology Internationalisation Partnership Award, ALS Malta Foundation and the University of Malta’s Research Trust.

Anyone who would like to participate in the study – whether they are an ALS patient or a ‘healthy’ person aged over 60 can get in touch on mnd.research@um.edu.mt