Sildenafil – the active ingredient also sold under the name Viagra – improves symptoms in patients with Leigh syndrome. This is currently cell This journal was co-authored by researchers from the Berlin Charité – Universitätsmedizin and a team from the Heinrich-Heine University of Düsseldorf (HHU), the University Hospital Düsseldorf (UKD) and the Fraunhofer Institute for Translational Medicine and Pharmacology ITMP in Hamburg. Leigh syndrome is a rare, previously untreatable metabolic disease that begins in childhood and causes severe neurological and muscular symptoms. In a preliminary study on six patients, sildenafil showed a positive effect on the course of the disease.
Leigh syndrome is a congenital disorder of the brain and muscles caused by defects in energy metabolism that often begins in infancy or early childhood. The disorder progresses slowly and can have severe symptoms, including seizures, muscle weakness, and paralysis, and may impair mental development. Patients with Leigh syndrome have a significantly shorter life expectancy and there are currently no approved drug treatments.
The real surprise: Energizing pills turn out to be effective
But now the researchers have identified a candidate drug that showed promising effects in pilot studies, and which may seem surprising at first glance: the so-called PDE-5 inhibitor sildenafil. This drug is best known for treating erectile dysfunction in adults. However, thanks to its vasodilatory properties, it is also used to treat pulmonary hypertension in infants. The study involved continuous administration of sildenafil to six patients with Leigh syndrome, ranging in age from 9 months to 38 years. In some cases, muscle strength improved and neurological symptoms disappeared in just a few months. In addition, they recovered faster from metabolic crises, that is, overload of energy metabolism, which can suddenly worsen the course of the disease.
“For example, in children treated with sildenafil, the walking distance increased tenfold, from 500 meters to 5,000 meters,” explains Professor Markus Schuelke. “In another child, this therapy completely suppressed a metabolic crisis that occurred almost every month, and in another patient he no longer suffered from epileptic seizures,” said Markus Schuelke, a physician-scientist at the Charité pediatric neurology department and one of the lead authors of the recently published study. He continued, stressing, “Such effects significantly improve the quality of life for Leigh syndrome patients. Although these initial observations need to be confirmed in more comprehensive studies, we are very pleased to have discovered a promising drug candidate for the treatment of this serious genetic disease.”
Why finding treatments for rare diseases is difficult
Such success cannot be taken for granted, as Leigh syndrome is rare, affecting only 1 in 36,000 children. “The small number of cases makes it difficult to study this disease and poses some obstacles in the urgent search for effective treatments,” explains Markus Schuelke. With such a small number of patients, large-scale studies are almost impossible, meaning experts from multiple centers will need to collaborate internationally. Additionally, brain and nerve tissue cannot simply be removed from a patient to investigate the cause of the disease.
To identify sildenafil as a potentially effective drug, researchers had to resort to several methodological tricks. As a first step, the researchers took skin cells from patients and used them to generate so-called induced pluripotent stem cells in the lab, cells that have the ability to grow into very different types of cells. From the stem cells, they cultivated metabolic nerve cells that exhibited the same dysfunction as the patient. In the next step, the researchers selected more than 5,500 active substances that were already approved to treat other diseases or for which extensive safety and efficacy data were available and tested their effects on cultured nerve cells.
Positive effects on cells, animal models, and patients
This is the largest drug screen for the treatment of Leigh syndrome to date. It showed that sildenafil, among other drugs, improved the electrical function of nerve cells. ”
Dr. Ole Pless, lead author of the ITMP study
Additional laboratory tests confirmed the results obtained at the cellular level. For example, in three-dimensional miniature replicas of the brain known as organoids, sildenafil stimulated the growth of nerve cells. The drug also improved energy metabolism and increased life expectancy in animal models.
Lead author Professor Alessandro Prigione, from UKD’s Department of General Paediatrics, Neonatology and Pediatric Cardiology, said: “Based on these results, we decided to administer the drug as part of an individual treatment trial to six patients with Leigh syndrome.” “Another decisive factor was the fact that detailed safety data on the long-term use of sildenafil in children were available, as the active ingredient in sildenafil was already approved for other pediatric diseases.” The first patient with Leigh syndrome was treated at Charité. Following positive results, additional patients were also treated in Düsseldorf, Munich and Bologna. All patients generally tolerated the drug well.
Comprehensive clinical studies are planned
Based on the results announced today, the European Medicines Agency (EMA) has granted sildenafil the status of Orphan Drug (ODD), meaning drug for orphan diseases. Such medicines can undergo a simplified approval process aimed at supporting the development of treatments for rare diseases. As a next step, the research team is planning a placebo-controlled clinical trial across Europe to validate the new findings and, assuming previous observations are confirmed, to prepare for the approval of sildenafil for Leigh syndrome. This study will be carried out as part of the SIMPATHIC EU project.
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Charité – Faculty of Medicine, University of Berlin
Reference magazines:
Zink, A. Others. (2026) Pluripotent stem cell-based drug discovery discovers sildenafil as a treatment for mitochondrial diseases. cell. DOI: 10.1016/j.cell.2026.02.008. https://www.cell.com/cell/fulltext/S0092-8674(26)00173-X
