Amyotrophic lateral sclerosis (ALS) is often considered a developmental disorder, but in rare cases, it begins in childhood or adolescence. This form, known as juvenile-onset ALS (JALS), is especially painful for affected children and families.
Several different genes can cause JALS when they are damaged. These genes encode proteins that are important for the normal functioning and survival of neurons – specialized nerve cells that transmit messages from the brain and spinal cord to the muscles, enabling movement, speech and breathing.
Children with JALS often have progressive muscle weakness and stiffness at an early age, gradually losing mobility and self-control. Unlike adult ALS, these children can live for decades with increasing disability, placing a significant emotional and financial burden on families and health systems. Despite this, JALS is still poorly understood, and there are no disease-modifying treatments.
A new research project by the University of Malta’s Motor Neuron Disease Lab aims to change that by combining human genetics with an advanced biological technique.
By analyzing the full DNA sequence of Maltese JALS patients, researchers are working to understand not only the underlying disease-causing mutation, but also other rare genetic factors that may influence how severe the disease is or how quickly it progresses. This approach reflects the growing recognition that even single-gene diseases are shaped by the broader human genetic background.
Integrating human genetics with an advanced biological model
At the same time, the project is introducing a new type of death using an unexpected ally: the fruit fly. Although small fruit flies share many important biological pathways with humans and have been used for more than a century to uncover the basics of this disease.
Importantly, this project looks beyond the visible signs. Using advanced technology, scientists will examine whether the changes that occur lead to molecular changes in the neurons. This molecular level insight may reveal new biological pathways involved in motor neuron survival – providing clues to future treatments not only for JALS, but potentially for adult ALS and related neurodegenerative diseases.
For families affected by JALS, progress cannot come soon enough. By combining a patient’s genome with new disease models, this research offers renewed hope that even rare diseases can be understood – and one day treated.
Ruben J Cauchi is professor of neurogenetics and head of the Motor Neuron Disease Lab at the University of Malta. Project juvenALS is funded by Science Malta through FUSION: The R&I Research Excellence Program 2025.
Photo: University of Malta ALS/MND Lab
Photo of the week
To understand the onset of pediatric ALS, researchers at the University of Malta are using fruit flies.
Shown here, a scientist gently transfers a fruit fly larva, a larva-like larva that later grows into an adult fly, from a plate of apple juice using a fine paint brush, preparing it for behavioral testing.
At this early stage, the nervous system is rapidly developing, which makes the larvae suitable for studying whether genetic changes interfere with motor neuron development. Despite their vulnerability, fruit fly larvae share important genetic pathways with humans, helping to reveal disease mechanisms for this rare childhood form of ALS.
Sound bites
• Until recently, spinal muscular atrophy (SMA) was a fatal motor neuron disease of childhood. That changed when scientists discovered a faulty gene and devised a way to correct the way the genetic message is read. Thanks to this breakthrough, many children diagnosed at an early age are now able to sit, walk and enjoy a very healthy life.https://www.nejm.org/doi/10.1056/NEJMoa1702752
• For the first time, researchers have treated prenatal SMA using a drug given to pregnant women. The child, who was born at risk of SMA, showed no signs of the disease after two years, suggesting that intervention during pregnancy may one day prevent the devastating loss of motor neurons.
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Did you know?
• Fruit flies (Drosophila melanogaster) share about 70% of genes associated with human disease, including many associated with neurodegeneration.
• Despite their size, flies have brains and nerves that control movement, learning and behavior.
• Flies grow and age rapidly, allowing for a rapid progression of neurodegenerative disease.
• Many major neurological discoveries, including the mechanisms of ALS, Parkinson’s and Alzheimer’s, were first identified in flies.
• Fly models enable genetic and drug testing that is not possible in humans or larger animals.
For more information, see: www.um.edu.mt/think
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