‘Viking’ link to Maltese ALS patient found in DNA study

A deleterious DNA change that is common in Scandinavia has been discovered in an elderly Maltese patient with amyotrophic lateral sclerosis (ALS).

ALS is a progressive neurological disease that attacks the 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.

In Malta, about one individual every month develops ALS. Some ALS patients die months after the onset of symptoms while others survive for years.

The finding is the latest of an ongoing study aimed at identifying genetic and environmental factors associated with ALS through data and blood samples collected from ALS patients in Malta. Recently, the team discovered that Maltese ALS patients have a unique genetic makeup compared to their European counterparts. Furthermore, manual labourers in Malta were found to be twice as likely to be diagnosed with ALS.

The research by the University of Malta, published in the European Journal of Human Genetics, identified a Maltese patient with ALS who had a flaw in the superoxide dismutase 1, or SOD1 gene – the first gene identified to cause ALS nearly three decades ago. The change substitutes an amino acid in the antioxidant enzyme produced by the gene, affecting its function in the nerves.

“The DNA variant that we have exposed is quite common in Scandinavia and Finland but relatively inexistent in the South of Europe. Our discovery has implications not only on the genetic cause of ALS in Malta and Gozo but also on the genetic heritage of the Maltese and Gozitan population,” lead researcher Prof. Ruben J. Cauchi, an associate professor of neurogenetics at the University of Malta, said.

The study therefore also raises the possibility that the conquest of the Maltese islands by Viking descendants originally headed by Count Roger, had left a lasting genetic mark on the island’s inhabitants.

“SOD1 D91A appears to have been a founder allele in Finno-Scandinavian populations, hence explaining the high allele frequency in Finland and northern Sweden, and the spread of the allele in Europe could be the result of Viking conquests,” the researchers said.

Viking invasions hundreds of years ago may be responsible for the spread of a genetic mutation associated with ALS. Researchers have also found that the most common genetic mutation found in ALS patients, the C9orf72 gene, seems to have originated in Northern Europe about 1,500 years ago, likely carried across Europe by Viking invaders from the 8th to 11th centuries.

In addition to confirming that genetic factors are partly to blame for ALS, the study gives hope to ALS patients found to carry SOD1 mutations. Groundbreaking gene-based treatments targeting SOD1 are presently at several different phases of clinical development. A large percentage of ALS patients worldwide with mutations in the SOD1 gene are expected to benefit from these therapies.

The national ALS Registry and Biobank at the University of Malta, set up with the aim of identifying and studying ALS patients and healthy volunteers, was key for this discovery. Blood samples donated by study participants remain stored in high-tech storage facilities at the University, allowing researchers to keep on making new discoveries even after the patients’ demise.

The study co-authors are Maia Farrugia Wismayer, Dr Andrew Farrugia Wismayer, and Prof Neville Vassallo from the University of Malta; and, Dr Adrian Pace from Karin Grech and Gozo General Hospitals.

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