Two international studies, with contribution from the University of Malta, published in the leading and journals have made groundbreaking discoveries on what causes amyotrophic lateral sclerosis (ALS) paving the way for treatments that block or delay this relentless disease.
ALS is a progressive neurological disease that destroys the nerves that interact with the body’s muscles. The disease erodes voluntary muscle movement, crippling the ability of patients to walk, talk, eat, and, eventually, breathe. Patients survive an average of three years after onset of first symptoms. Malta has one of the highest incidence rates of ALS in Europe.
Researchers collaborating on Project MinE, a large international initiative aiming at defining the genetic basis of ALS, have discovered several genes that increase disease risk. More than a dozen genes were found to cause ALS because their code is disrupted from birth. However, more than 40 different genes can be switched either on or off by environment and lifestyle factors during the lifetime of a person increasing the risk of developing ALS.
The studies are a monumental effort, involving thousands of ALS patients and normal subjects worldwide. Five years ago, the University of Malta set up a National ALS Registry and Biobank to identify and recruit ALS patients for this international endeavour coordinated by Professor Jan Veldink from the University of Utrecht in The Netherlands.
“Combined together, the results of our studies implicate genes that are either directly or indirectly involved in cholesterol synthesis, and this is the most surprising discovery”, explained Professor Ruben Cauchi, from the Faculty of Medicine & Surgery at the University of Malta, who is leading the Malta team within Project MinE.
ALS patients profiled in both studies had differences in cholesterol levels compared to normal subjects. Cholesterol is known to be regulated by ‘autophagy’, a process that cells use to remove damaged material. Cells collect their trash in ‘garbage bags’ known as vesicles. Crucially, vesicles need to be transported to collection points within the cell to be either destroyed or recycled.
Genes that regulate autophagy and vesicle-mediated transport are most likely to be corrupted in ALS patients. Right now, making use of animal models of disease, researchers are working on the link between the cell’s garbage collection mechanism, cholesterol and ALS which can be potentially exploited for development of therapies.
Research at the Motor Neuron Disease Laboratory at the University of Malta is presently funded by the University of Malta Research Excellence Fund, the Malta Council for Science & Technology and the University of Malta’s Research Trust (RIDT).
Research at the Motor Neuron Disease Laboratory at the University of Malta is presently funded by the University of Malta Research Excellence Fund, the Malta Council for Science & Technology and the University of Malta’s Research Trust (RIDT).
