The active ingredient in the erectile dysfunction drug Viagra has shown unexpected promise as a potential treatment for a rare and fatal childhood disease, offering new hope where no approved therapies currently exist.
German researchers report that sildenafil, the compound that makes Viagra work, improved symptoms in six patients with Leigh syndrome, a severe genetic disorder. Over months of treatment, patients saw gains in muscle strength, neurological function, and metabolic stability.
From ED drug to potential lifeline
The connection emerged from one of the largest drug screenings for Leigh syndrome to date, where researchers from Charité – Universitätsmedizin Berlin and Heinrich Heine University Düsseldorf tested over 5,500 compounds. Sildenafil emerged as a leading candidate, a finding researchers then tested in laboratory models and a small human pilot study.
In the study, patients aged between nine and 38 took daily, low-dose sildenafil for periods of up to seven years. The doses, ranging from 0.66 to 3 milligrams, are a fraction of a standard Viagra pill. The results, published in the journal Cell, were striking.
“For example, in the case of a child undergoing sildenafil treatment, the walking distance increased tenfold, from 500 to 5,000 meters,” said lead researcher Dr. Markus Schuelke of Charité in a statement. He noted other individual improvements, including the complete suppression of almost monthly metabolic crises in one child and the cessation of epileptic seizures in another.
How a blood-flow drug might combat a cellular energy crisis
Leigh syndrome is not a vascular disorder but a primary mitochondrial disease. It is caused by mutations in over 110 different genes that disrupt the mitochondria, the power plants of the cell. This leads to a catastrophic energy deficit, particularly in the brain and nerves, resulting in progressive neurodegeneration.
The potential benefit of sildenafil lies in its well-known mechanism as a PDE-5 inhibitor, which increases blood flow. Researchers, including Professor Dr. Alessandro Prigione of University Hospital Düsseldorf, theorise that by improving circulation, the drug may enhance the delivery of oxygen and nutrients to tissues starved of energy by faulty mitochondria. This improved blood flow is particularly significant for addressing pulmonary hypertension—a dangerous complication of Leigh syndrome affecting the lungs, heart, and kidneys.
Preclinical evidence supports this. The team observed that sildenafil improved energy metabolism in lab-grown models, including brain organoids created from patient cells. In animal studies, rodents and pigs with Leigh syndrome lived longer after treatment; two of seven pigs with fatal cases survived for more than two months, with one remaining stable for six months.
The brutal reality of Leigh syndrome
The urgency for a treatment is acute. Leigh syndrome affects approximately 1 in 36,000 children globally, with a higher incidence in regions like Quebec, Canada, and the Faroe Islands. According to the US National Institutes of Health, half of children born with the disease die before the age of three.
Symptoms typically appear in infancy or early childhood and can include vomiting, seizures, severe muscle weakness, difficulty swallowing, and developmental delays. The Child Neurology Foundation states that while some individuals have a milder, more stable course, many experience rapid neurological decline. Diagnosis is currently made via MRI scans and blood tests, though researchers at Virginia Tech University have recently identified a brain signal that could aid earlier detection.
The path to a licensed treatment
Encouraged by the pilot data, Dr. Schuelke and colleagues are planning a Europe-wide, placebo-controlled clinical trial to definitively test sildenafil’s efficacy and safety. This trial will form part of the SIMPATHIC EU project. The drug has a significant advantage: its safety profile in children is already established, as it is approved for paediatric pulmonary hypertension.
Furthermore, the European Medicines Agency (EMA) has granted sildenafil Orphan Drug Designation for Leigh syndrome, a status that incentivises and streamlines the development of treatments for rare diseases.
The search for treatments is increasingly coordinated internationally. Organisations like The Lily Foundation in the UK are part of the Leigh Syndrome International Consortium, a global patient-driven network that has pledged significant funding to accelerate research, reflecting a growing collaborative effort to combat this devastating condition.