Submitted by lac59 on Tue, 25/08/2026 - 16:50
Scientists at the University of Cambridge, alongside international collaborators, have published a paper in Nature Communications revealing the first induced pluripotent stem cell model for MELAS syndrome.
MELAS syndrome is a rare mitochondrial disorder that causes stroke-like episodes, dementia and muscle weakness, with symptoms often beginning in childhood or early adulthood. There is currently no cure for MELAS and further research is desperately needed.
For the first time, the research group has grown models of human brain tissue (called cortical organoids) using stem cells derived from patients with a specific genetic mutation labelled ‘m.3243A>G’. This common mutation in mitochondria is the leading cause of MELAS.
By analysing these organoids, the researchers discovered that neurons located deep within the brain's cortex are uniquely vulnerable to mitochondrial dysfunction.
Mitochondria are the ‘power stations’ of the cell and when they go awry it can cause cells to lose energy. In the study, when the observed neurons lost energy, their axons (the projecting arms that carry signals within the brain) began to wither away, ultimately causing the cells to die.
This study gives us a much clearer picture of exactly how mitochondrial diseases damage the human brain and has provided a powerful new tool to test potential treatments in future.
The lead authors on the paper were Dr Denisa Hathazi, Dr Andras Lakatos and Prof Rita Horvath, from the Department of Clinical Neurosciences.
Dr Hathazi commented: “This study is important for the mitochondrial disease community because m.3243A>G is the most common pathogenic mitochondrial DNA mutation, yet there is currently no animal model. Our human brain organoid model provides a unique way to study how this mutation affects different brain cells and why some neurons are particularly vulnerable.
We hope this model will help us better understand MELAS and other mitochondrial diseases and ultimately lead to better treatments for patients.”
