For most of his young life, the boy could walk only about 500 meters before his legs gave out. Then he started taking sildenafil.
Six months later, he covered 5 kilometers. Ten times farther, without stopping.
That single anecdote anchors a paper published March 11, 2026, in Cell (doi: 10.1016/j.cell.2026.02.008) by researchers at Charite University Hospital Berlin, Heinrich Heine University Dusseldorf, and collaborators across Europe. Sildenafil, the active ingredient in Viagra, improved walking distance tenfold in one patient with Leigh syndrome, a rare and almost uniformly fatal mitochondrial disease that typically kills children before they reach their tenth birthday. According to EurekAlert, the boy had been limited to roughly 500 meters; after treatment, he walked 5,000. The paper's co-lead authors are Markus Schuelke of Charite and Alessandro Prigione of Heinrich Heine University.
Leigh syndrome affects roughly one in 36,000 to 40,000 live births, according to EurekAlert. Children born with it inherit defective mitochondrial DNA that prevents their cells from producing adequate energy. The result is progressive neurological decline: loss of motor function, seizures, metabolic crises, respiratory failure. There is no approved treatment. Families manage symptoms until the disease takes everything.
The sildenafil result is not a cure. It is not even close to a cure. But it is something that has never existed before for this disease: a signal, in six patients, that the right compound might exist.
The signal came after one of the largest drug repurposing screens ever run against a mitochondrial disorder. The team at Heinrich Heine University and the University of Cologne tested 5,632 compounds already approved for other conditions, according to a preprint posted to medRxiv. They used patient-derived stem cells reprogrammed into neural cells, looking for compounds that could restore the mitochondrial membrane potential that MT-ATP6 mutations disrupt. Phosphodiesterase 5 (PDE5) inhibitors emerged as the strongest hits. Sildenafil is a PDE5 inhibitor.
The mechanism is not fully understood. PDE5 inhibitors were developed to relax blood vessels for erectile dysfunction and pulmonary hypertension. That the same pathway might shore up failing mitochondria in brain cells is, as the researchers themselves acknowledge, unexpected. Mitochondria in neurons appear to share enough signaling architecture with vascular smooth muscle that a blood pressure drug can reach them. The preprint describes how sildenafil restored mitochondrial membrane potential in MT-ATP6 cells and improved function in mammalian models. Separately, sildenafil extended lifespan in mouse and pig models of Leigh syndrome, according to Science. Two of seven treated pigs survived more than two months; one remained stable for six months.
Six patients took sildenafil for between 18 months and seven years, according to Science. Ages ranged from nine months to 38 years. All had confirmed MT-ATP6 mutations, the genetic subtype the screen was designed to address. One child had suffered metabolic crises almost monthly before starting treatment; the crises stopped entirely on sildenafil, according to EurekAlert. Another patient stopped having epileptic seizures. One patient discontinued treatment due to a rash. Four of the five remaining patients showed some improvement in movement ability. Two showed small improvements in cognitive areas such as language perception.
The European Medicines Agency granted sildenafil orphan drug designation for Leigh syndrome in March 2026, designation EU/3/23/2831, according to PubMed. Orphan status does not confirm efficacy. It means the disease is rare enough and the commercial incentive low enough that the EMA will fast-track review if evidence accumulates.
Simon Johnson, a Leigh syndrome researcher at Northumbria University who was not involved in the study, urged caution. The effects in animal experiments appear small, he told Science. The clinical data comes from six people. The evidence for beneficial effects, he argued, is not yet compelling. The drug does look safe. That is the good news.
The trial planned next is larger. Researchers in the SIMPATHIC consortium, a European Horizon project, are designing a multinational placebo-controlled trial targeting 60 to 70 patients across several European countries, according to Radboud University Medical Center. The CureMILS consortium, funded through the European Joint Programme for Rare Diseases, is also involved.
The deeper question the paper raises is not why sildenafil works. It is why nobody tried it sooner. PDE5 inhibitors have been on the market since 1998. Leigh syndrome was described in 1951. The gap between approved drug and rare pediatric disease is not scientific. It is economic. Drug developers pursue large markets. Rare pediatric mitochondrial diseases offer none. The screen the team ran was only possible because of patient-led advocacy and consortium funding. Without the structural incentive that patient groups and public grants provide, the 5,632 compounds never get tested against diseases that affect one in 40,000 births.
That is the part of this story worth sitting with. The drug that might help a child survive long enough to learn to read was sitting on pharmacy shelves for 28 years before anyone thought to look. What else is sitting there?
A Phase II trial will answer whether the signal holds. If it does, sildenafil or a related PDE5 inhibitor could become the first targeted therapy for MT-ATP6-related Leigh syndrome. If it does not, six patients will have offered the field the most informative failure it has ever had.
