Leigh syndrome is a mitochondriopathy, meaning it affects energy production in cells. Symptoms include muscle weakness, difficulty swallowing, breathing issues, seizures, and delayed mental development. Low case numbers make it difficult to conduct research on the disease and to find new, effective therapies.
In the current study, researchers carried out the largest drug screening for the condition to date. They tested over 5,500 compounds that have either already been approved in Europe or have strong safety data on diseased nerve cells, ultimately identifying sildenafil, also known as Viagra, as a promising candidate.
They next tested sildenafil in brain organoids, where it was found to promote nerve cell growth. They also tested it in animal models, where it improved energy metabolism and lengthened lifespan.
These results led the researchers to consider the drug’s effects on human patients. They thus administered it as part of an individual therapeutic trial on six patients with the condition who were between 9 months and 38 years old.
Within a few months, patients had stronger muscles, and some saw improvements in neurological symptoms. Patients also recovered quickly from metabolic crises such as overloads of energy metabolism.
"In the case of a child undergoing sildenafil treatment, the walking distance increased tenfold, from 500 to 5,000 meters. In another child, the therapy completely suppressed metabolic crises that occurred almost monthly, while another patient no longer suffered from epileptic seizures,” said study author, Prof. Markus Schuelke, a physician and scientist at the Department of Pediatric Neurology at Charité University of Medicine Berlin Department of Pediatric Neurology, Germany, in a press release.
He added that while they are happy to have found a promising drug candidate for the condition, further research is needed to confirm these initial results in a more comprehensive study.
Sources: Science Daily, Cell
