A study in Germany has identified a potential treatment for Leigh syndrome, with early positive results in children supported by findings in cells from patients, mice and pigs.
Leigh syndrome is a rare and severe childhood disorder that affects energy metabolism, leading to symptoms such as seizures, muscle weakness, developmental delay and paralysis. There are currently no treatments that alter the course of the disease.
A team of researchers led by EARA member Charité Universitätsmedizin Berlin first screened over 5500 drugs already approved for other conditions using patient-derived nerve cells and brain organoids which show key disease features, such as impaired energy production and disrupted cell growth. Sildenafil, the drug known as Viagra, emerged as the most promising candidate, restoring cell metabolism and supporting nerve cell growth.
Markus Schuelke, from Charité and co-lead author of the study published in Cell, said, "The low case numbers make it difficult to research the disease and present some obstacles in our urgent search for effective therapies.”
To address this challenge, the team then tested the drug in mice and pigs genetically modified to specifically develop symptoms of Leigh syndrome. Animals treated with sildenafil showed increased lifespan, improved muscle strength and fewer energy overload crises, which are key drivers of disease progression.
Building on these findings, six children with Leigh syndrome were treated with sildenafil. The patients showed improved motor skills, with walking distance increasing tenfold, from 500 to 5000 meters, and greater resistance to energy crises. A more comprehensive study is already being planned.
The European Medicines Agency has since designated sildenafil as an orphan drug – a status granted to drugs for rare conditions that contributes to faster review, reduced fees and 10 years of market exclusivity to encourage its use in rare diseases.