Photo: Times of Malta/Chris Sant Fournier 

University of Malta researchers have discovered a potential new drug target for amyotrophic lateral sclerosis (ALS), raising hopes for the development of therapies that target a broad spectrum of patients. The study will be published in the Neurobiology of Aging journal.

ALS is a progressive neurological disease affecting the nerves that control the muscles of the body. Due to the disease, muscles stop functioning leading to difficulties with walking, talking, eating, and, eventually breathing. The genetics of Maltese puts the population at a greater risk of developing ALS. Incidence rate of the disease in Malta is therefore greater than the European average.

In the study, researchers switched off the gene SCFD1 in fruit flies to discover that this triggered ALS symptoms. Similar to patients, the organisms developed reduced mobility and a deterioration of the contact points between nerves and muscles. Flies are used in ALS research because of considerable genetic and biological similarities to humans.

“The SCFD1 gene is one of the strongest risk factors for ALS patients globally. However, the significance of the connection between SCFD1 and the disease has remained unknown,” explained the head of the Motor Neuron Disease Laboratory at the University of Malta, Prof. Ruben J. Cauchi.

SCFD1 popped up on the radar of ALS genetics in a recent monumental study that scrutinized the genes of hundreds of thousands of ALS patients and healthy volunteers worldwide. The initiative was spearheaded by the Project MinE international consortium, of which Malta is a member.

“These gigantic studies have the power to discover genes that are commonly altered in ALS patients compared to those without the disease. However, their unbiased approach means that they often churn out genes whose link to ALS remains ambiguous,” enlightened Prof. Cauchi.

When scouting for molecular defects in cells in which SCFD1 was switched off, University of Malta researchers found that the cell’s ability to fold proteins is compromised. Proteins need to be correctly folded into complex 3D structures to perform their vital functions.

It is well known that nerves already have a suboptimal ability to fold proteins correctly and factors that dampened this further are expected to increase susceptibility to ALS. This includes alternations that damage the SCFD1 gene. Repairing or activating SCFD1 in patients is thus expected to slow or stop their disease.

The research team know that they are on the right track because in a historic first, a drug that targets protein misfolding is set to be available to European ALS patients after a hiatus of 27 years. This year, the European Medicines Authority (EMA) is expected to approve AMX0035 (Relyvrio), essentially confirming the decision by the Food and Drug Administration (FDA), its equivalent in USA, last year.

Study co-authors are Dr Rebecca Borg, Angie Purkiss, Rebecca Cacciottolo and Dr Paul Herrera.

Research at the Motor Neuron Disease Laboratory at the University of Malta is presently funded by the Malta Council for Science & Technology Research Excellence Programme, a Tertiary Education Scholarship, and the Anthony Rizzo Memorial ALS Research Fund facilitated by the University of Malta’s Research Trust (RIDT).