SINGAPORE – An international study has discovered that people living with the neurodegenerative condition Spinal Muscular Atrophy (SMA) are at higher risk of developing fatty liver disease, suggesting that SMA patients may face additional health problems over time. This finding raises significant concerns about long-term care and health outcomes for individuals with SMA.
SMA is a rare genetic condition that prevents the body from producing Survival Motor Neuron (SMN), a protein essential for nerves that control movement. The damaged motor neurons are unable to send messages to the muscles, resulting in progressive muscle weakness. While recent advances in treatment have improved survival rates, particularly for babies with severe SMA, this new research indicates that the impact of SMA extends beyond the nervous system, potentially affecting other organs such as the liver.
Fatty liver disease, usually linked to heart conditions, diabetes, and obesity, is a condition in which fat builds up in the liver, causing inflammation and damage. The presence of fatty liver disease in mild and severe forms of SMA is particularly concerning, as it can have serious long-term consequences for the health of SMA patients in childhood and adulthood.
The multi-centre study, published in the prestigious Journal of Clinical Investigation (May 2024), involved clinicians and researchers from leading institutions across Singapore, the United States, and Scotland, including the Agency for Science, Technology and Research (A*STAR), Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine),Boston Children’s Hospital, Harvard Medical School, Harvard University, and the University of Aberdeen.
The study revealed that the genetic mutation responsible for SMA reduces SMN protein levels in liver cells, impairing their ability to break down and use fat effectively. This finding explains the presence of fatty liver disease in SMA patients, which was detected in children as young as three years old through liver ultrasound scans. Crucially, editing the faulty gene in patients' stem cells to increase SMN production reversed the liver dysfunction caused by the mutation, establishing a direct link between the genetic defect and liver problems in SMA.
"Our findings show that SMA patients may be at higher risk of additional health problems over time, as the SMA gene mutation also affects other organs in the body, including the liver," said Dr Crystal Yeo, director of this research and Clinician-Scientist who directs the Translational Neuromuscular Medicine Laboratory at A*STAR’s Institute of Molecular and Cell Biology (IMCB). Dr Yeo is also a practicing Consultant Neurologist at National Neuroscience Institute (NNI).
“Since SMA patients are living longer, knowing that SMA affects other organs changes how doctors monitor and treat this condition,” says Prof Basil Darras, Chief of the Division of Clinical Neurology and Director of the Neuromuscular Center and SMA program from Boston Children’s Hospital and Harvard Medical School.
International collaborators Prof Simon Parson, Regius Chair of Anatomy from the University of Aberdeen, Prof Lee Rubin, co-Director of the Harvard Nervous System Diseases Program at Harvard University, and Prof Ong Wei Yi, Professor of Anatomy at NUS Medicine and NUS Life Sciences Institute, agree that while we now have life enhancing therapies for those affected by SMA, it is key that we understand which illnesses might affect these patients in future.
The study's findings underscore the importance of viewing SMA as a multi-organ disorder and the need for a comprehensive approach to patient care. As individuals with SMA live longer due to improved treatment options, understanding the long-term effects of the genetic mutation on various organs becomes crucial for screening for previously unknown problems, developing effective treatment strategies and improving patient outcomes, such as survival and quality of life. Further research in this area could not only benefit those living with SMA but also provide insights into the treatment of other neurological conditions with similar disease mechanisms.
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About A*STAR Institute of Molecular and Cell Biology (IMCB)
The A*STAR Institute of Molecular and Cell Biology (IMCB) is a premier research institute whose mission is to harness biology for transformational bio-therapeutics and diagnostics. With a strong emphasis on collaboration with stakeholders across the ecosystem in Singapore, IMCB aims to achieve scientific excellence and continues to nurture the next generation of scientists in order to create growth and enhance lives. For more information about IMCB, please visit www.a-star.edu.sg/imcb.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.
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About the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine)
The Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), is Singapore’s first and largest medical school. Our enduring mission centres on nurturing highly competent, values-driven and inspired healthcare professionals to transform the practice of medicine and improve health around the world.
The School is the oldest institution of higher learning in the National University of Singapore and a founding institutional member of the National University Health System. It is one of the leading medical schools in Asia and ranks among the best in the world (Times Higher Education World University Rankings 2024 by subject and the Quacquarelli Symonds (QS) World University Rankings by subject 2023). For more information, visit https://medicine.nus.edu.sg/
About the University of Aberdeen
Established in 1495, and named Scottish University of the Year 2019, the University of Aberdeen is the fifth oldest in the UK and is consistently ranked in the top 200 of the world’s universities.
The University is renowned for its world-leading research in health, energy, food and nutrition and environmental and biological sciences. The University also has an outstanding track-record for arts and humanities research.
With a community of students and staff encompassing 130 nationalities, the University of Aberdeen has a global outlook and reach.
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