Until recently, amyotrophic lateral sclerosis (ALS) was a relatively unknown disorder which was poorly understood by the scientific community. Awareness campaigns such as the Ice Bucket Challenge greatly changed this and set the ball rolling for a greater number of scientists around the world to attempt to understand the causes of this devastating disease.

A typical fruit fly lab station. Flies are anaesthetised using a carbon dioxide gun and viewed using a stereomicroscope. If needed, they are gently moved around using a paintbrush. Photo: Maia Farrugia Wismayer

ALS is a life-altering disorder. It leads to the death of nerve cells in the brain and spinal cord, resulting in sufferers experiencing a drastic loss of mobility. The disease is progressive, meaning patients experience worsening of symptoms and spreading to different regions of the body. Unfortunately, ALS is a fatal condition for which there is currently no effective treatment. Research aiming to understand the causes of this disease is crucial for the development of new therapies.

Research has revealed that the vast majority of ALS cases arise through an interplay between an individual’s genetic predisposition to this disease and exposure to various environmental risk factors. As part of a team of scientists within the University of Malta’s ALS research group, my doctoral studies, supervised by Ruben Cauchi, aim at uncovering the genetic defects which contribute to ALS in Maltese patients, along with the environmental factors that increase the risk of this disease in genetically susceptible individuals. To date, our team has discovered that the risk of developing ALS is greater in individuals that have physically strenuous jobs. Another discovery is that genetic defects in Maltese ALS patients are unique compared to those found in patients overseas.

Part of our research involves the use of the fruit fly to study the effects of ALS-associated genetic defects. Despite their drastically different appearances, fruit flies and humans share approximately 75 per cent of disease-related genes, making this tiny insect ideal for research on human diseases. Fruit flies reproduce at a rapid rate, enabling scientists to investigate the effects of genetic mutations over multiple generations in short periods of time. Finally, there are no ethical issues associated with using the fruit fly as a model organism for research. This humble organism will help us fulfil the ultimate aim of our research; that of developing gene therapies tailored to local patients, providing a ray for hope for individuals suffering from this cruel disease.

The research work disclosed in this publication is partially funded by the Endeavour Scholarship Scheme (Malta). Scholarships are part-financed by the European Union – European Social Fund (ESF) – Operational Programme II – Cohesion Policy 2014-2020 ‘Investing in human capital to create more opportunities and promote the well-being of society’.

Maia Farrugia Wismayer, PhD student, biomedical scientist

Sound bites

• Blue-green algae (cyanobacteria) have been shown to produce a compound which is neurotoxic. This toxin was found to accumulate in various forms of marine wildlife, including shellfish, sharks and fish. In populations which consume high levels of this dietary toxin, the incidence of ALS was significantly higher than that in populations where such food sources were not dietary staples. This toxin is thought to contribute to ALS development by incorporating itself into an antioxidant enzyme, causing this protein to misfold into a conformation that is toxic to motor neurons, leading to their degeneration.

https://www.sciencedaily.com/releases/2019/09/190917115449.htm

• Defects in the scaffold which maintains the structural integrity of nerve cells have been linked to ALS. This scaffold, termed the cytoskeleton, provides a crucial framework which allows important molecules to be transported along the nerve cell. Mutations in a number of genes may lead to defects in the cytoskeleton, which in turn may lead to neuronal transport defects. This impairs the ability of nerve cells to communicate with one another, potentially leading to neurodegeneration. Genes which may disrupt cytoskeletal function were identified through large-scale studies, including thousands of patient and control subjects.

https://www.sciencedaily.com/releases/2018/03/180321121618.htm

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Did you know? 

• Female fruit flies are capable of laying up to 500 eggs during their lifetime.

• The average person has approximately 400 genetic mutations, the majority of which do not cause disease.

• Despite sharing 75 per cent of disease-related genes with humans, fruit flies only have four chromosomes compared to the 46 found in human cells.

• Approximately five per cent of the human genome consists of viral sequences which have accumulated over the course of evolution.

For more trivia see: www.um.edu.mt/think