Summary: Scientists have discovered that mutations in the EPG5 gene\u2014known for causing the rare childhood disorder Vici syndrome\u2014also increase the risk of Parkinson\u2019s disease and dementia later in life. The gene plays a crucial role in autophagy, the process by which cells clear out damaged material.<\/p>\n
When this system fails, harmful proteins build up, damaging nerve cells over time. The study reveals a direct biological link between early neurodevelopmental disorders and late-onset neurodegenerative diseases, offering hope for shared therapeutic targets.<\/p>\n
Key Facts:<\/p>\n
Shared Mechanism: EPG5 mutations disrupt autophagy, connecting rare childhood disorders to adult neurodegeneration.Broader Effects: Individuals with EPG5 errors can develop Parkinson\u2019s or dementia in adolescence or adulthood.Therapeutic Insight: Findings highlight how studying ultra-rare diseases can guide treatments for common neurological conditions.<\/p>\n
Source: King\u2019s College London<\/p>\n
Errors in a gene known to cause a serious neurodevelopmental condition in infants are also linked to the development of Parkinson\u2019s disease in adolescence and adulthood, according to new research.<\/p>\n
The study, published in the\u00a0Annals of Neurology, looked at a gene called\u00a0EPG5.\u00a0Errors in this gene are already known to cause Vici syndrome \u2013 a rare and severe inherited neurodevelopmental condition that presents early in life and affects multiple organ systems.<\/p>\n
Now researchers at King\u2019s College London, University College London (UCL), the University of Cologne and the Max Planck Institute for Biology of Ageing have found that errors in the same gene are linked to changes in nerve cells that lead to more common age-related conditions like Parkinson\u2019s disease and dementia.<\/p>\n
Professor Heinz Jungbluth, Professor of Paediatric Neurology at King\u2019s College London and lead and co-senior author of the study, said: \u201cThis research, supported by patient organisations, was prompted by our earlier observation of an apparent increased Parkinson\u2019s disease risk in relatives of children with Vici syndrome, after our team at King\u2019s had found\u00a0EPG5\u00a0to be a driver of this condition.<\/p>\n
\u201cOur work shows that, whilst rarely considered a priority, research into (ultra)rare conditions such as Vici syndrome (where fewer than 10 children are currently known to have the condition in the UK) may provide vital insights into much more common disorders and have substantial public health benefits.\u00a0<\/p>\n
\u201cUnderstanding the causes of these devastating and often life-limiting diseases is essential for therapy development and thus offers hope for patients and their families.\u201d\u00a0<\/p>\n
In the largest study of its kind to date, the team of scientists analysed clinical and genetic data from 211 individuals from across the world with rare errors in\u00a0EPG5. They found that the effects of these genetic errors are broader and more variable than previously known \u2013 while some individuals had life-limiting forms of Vici syndrome identified before or shortly after birth, others showed much milder symptoms, including delay in movement, speech, and learning.<\/p>\n
The researchers also discovered that some of the patients included in the study went on to develop a breakdown of nerve cells in adolescence or early adulthood that led to Parkinson\u2019s disease and dementia. Brain scans analysed in some cases showed additional iron build-up in the brain, a feature of other, closely linked neurodevelopmental disorders.<\/p>\n
Dr Reza Maroofian, co-first author of the study from the UCL Queen Square Institute of Neurology, said: \u201cOur findings link\u00a0EPG5\u00a0dysfunction to Parkinson\u2019s disease, highlighting how neurodevelopmental and neurodegenerative disorders can be mechanistically interconnected and add to a growing list of such conditions.<\/p>\n
\u201cThis study underscores how insights from rare paediatric brain disorders can inform our understanding of more common adult-onset neurodegenerative diseases, such as Parkinson\u2019s and dementia.\u201d<\/p>\n
The\u00a0EPG5\u00a0gene is involved in an important cellular process called autophagy, where the cell breaks down unwanted or damaged components and either recycles them into new parts or disposes of them. The protein made by\u00a0EPG5\u00a0is involved in the last stage of this process \u2013 attaching the parts for disposal to the cell\u2019s waste disposal unit for removal from the cell.<\/p>\n
To explore the biology underpinning their findings, the researchers used patient-derived cells and model organisms, including mice and the tiny roundworm\u00a0C. elegans, and introduced errors into\u00a0EPG5.<\/p>\n
These experiments showed that genetic errors in the gene disrupt the cell\u2019s ability to clear damaged components from the cell, leading to the build-up of proteins closely associated with Parkinson\u2019s disease.<\/p>\n
Professor Jungbluth, who is also a Consultant Paediatric Neurologist at Evelina London Children\u2019s Hospital, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust, said: \u201cUsing the example of\u00a0EPG5, our findings suggest a life-time continuum of early-onset neurodevelopmental and late-onset neurodegenerative disorders, and more specifically an intriguing link between aberrant nerve development and degeneration linked in the same fundamental cellular mechanism preserved throughout different species.\u201d<\/p>\n
Dr Manolis Fanto, Reader in Functional Genomics at King\u2019s College London and co-senior author of the study, added: \u201cThis project highlights the importance of collaboration between basic and clinical neuroscientists to unravel the complex mechanistic consequences of inherited genetic conditions throughout all life stages.\u201d<\/p>\n
The study provides new understanding of how errors in autophagy can underpin a range of lifelong neurological conditions and may help pave the way for future treatments that target these shared drivers of disease.<\/p>\n
Key Questions Answered:Q: What is Vici syndrome?<\/p>\n
A: Vici syndrome is a rare inherited neurodevelopmental disorder caused by mutations in the EPG5 gene. It affects multiple organ systems, including the brain, muscles, heart, and immune system, leading to severe developmental delays and other complications that usually appear early in life.<\/p>\n
Q: What did researchers discover about the EPG5 gene?<\/p>\n
A: Errors in EPG5, long known to cause Vici syndrome in infants, are also linked to Parkinson\u2019s disease and dementia in later life.<\/p>\n
Q: How does EPG5 affect the brain?<\/p>\n
A: EPG5 controls how cells dispose of damaged material; when disrupted, proteins accumulate and harm neurons, leading to neurodegeneration.<\/p>\n
Q: Why is this study important?<\/p>\n
A: It bridges the gap between rare pediatric brain disorders and widespread adult diseases, revealing shared biological pathways that could be targeted by new treatments.<\/p>\n
About this Parkinson\u2019s disease, Vici syndrome, and genetics research news<\/p>\n
Author: Joanna Dungate<\/a>
Source: King\u2019s College London<\/a>
Contact: Joanna Dungate \u2013 King\u2019s College London
Image: The image is credited to Neuroscience News<\/p>\n