A study found that Viagra, a drug for erectile dysfunction, could treat Leigh syndrome, a rare genetic disease. Animal experiments showed a life-extending effect, and some patients also improved. The number of patients in the study was small, making it too early to say the treatment is definitive, but it was seen as offering new hope to patients in a field with no established therapies.
A team led by Alessandro Prigione at the University of Düsseldorf said on the 11th (local time) in the journal Cell that sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, improved mitochondrial dysfunction and restored neurodevelopmental pathways in brain Organoids made from the cells of patients with Leigh syndrome. Animal experiments also confirmed a life-extending effect.
◇Correction of mitochondrial mutations
Leigh syndrome is a rare genetic disorder that causes central nervous system damage, occurring in about 1 in 40,000 people. It was first reported in 1951 by Archibald Denis Leigh, a British neuropsychiatrist, from whom it takes its name. It arises when problems occur in mitochondria, the cellular organelles that produce energy in the body. Seventy-five percent of patients die at ages 2 to 3 from breathing difficulties and heart failure, and there is currently no established treatment.
The team sought drugs to improve dysfunction caused by mutations in the MT-ATP6 gene in the mitochondria of patients with Leigh syndrome. This gene makes a protein needed for mitochondria to use oxygen. Mitochondria produce energy using oxygen, and when this process is damaged, oxygen accumulates and instead harms cells.
Screening about 6,000 already approved drugs, the researchers found that a compound known as a PDE5 inhibitor was effective at restoring mitochondria to normal. PDE5 inhibitors are the active ingredients in erectile dysfunction drugs such as sildenafil, tadalafil (brand name Cialis), and vardenafil (Levitra). They sustain erections by preventing blood from draining from peripheral vessels in the penis. Of these, sildenafil showed the most pronounced therapeutic effect, the team said.
◇Effective from Organoids to animals and humans
The team first tested the drug in cells. They reprogrammed patients' cells into induced pluripotent stem cells (iPS cells). iPS cells are fully grown cells reverted to an embryonic stem cell state by inserting specific genes or proteins. Depending on conditions, iPS cells can grow into any cell of the human body.
To model central nervous system abnormalities in patients with Leigh syndrome, the team created brain Organoids from iPS cells. Organoids are stem cells cultured into three-dimensional structures resembling organs and are called mini-organs. When sildenafil was administered to brain Organoids made from patient cells, genes involved in neurodevelopment were activated. The imbalance in neuronal cell types seen in patients with Leigh syndrome was also partially corrected.
The animal results were more definitive. Sildenafil extended the lifespan of mice carrying the mutant gene causing Leigh syndrome. Pigs with a similar mutation usually die within a few weeks, but after sildenafil treatment, 2 of 7 survived for more than two months. One remained stable for up to six months.
Finally, sildenafil was tested in actual patients. The team administered sildenafil to six patients with an MT-ATP6 mitochondrial mutation, from 9 months old to 38 years old. Co-corresponding author Markus Schuelke of Charité University Hospital said, "A 16-year-old patient has been taking sildenafil for more than seven years," adding, "The patient still cannot walk alone, but symptoms improved when measured by standard clinical scales."
The remaining five took sildenafil for between a year and a half and seven years. One stopped due to a rash, but the other four showed improved motor function, the team said. Two also had slight gains in cognitive abilities such as language comprehension.
◇Large-scale clinical trial to start at the end of the year
Academia reacted mixed to the results. Vivian Gama, a cell biologist at Vanderbilt University, told Science that it was "a really exciting paper" and said that multiple lines of evidence "suggests" sildenafil could be a truly promising compound for one of the most lethal pediatric rare diseases.
However, Simon Johnson, a Leigh syndrome researcher at Northumbria University in the United Kingdom, said, "The effects in animal experiments appear modest, and the clinical data come from a very small number of patients," adding, "While it is encouraging that the drug appears safe, the evidence for efficacy is not very compelling." Gama also agreed that human data are difficult to interpret, but noted that it is hard to recruit patients with the rare disease Leigh syndrome.
The team said it will launch a large-scale clinical trial at the end of the year in several European countries with 60 to 70 participants. The finalization of the trial protocol and ethics committee approval remain, but the researchers are optimistic about clearing those steps. Above all, they emphasized that sildenafil is a drug whose efficacy and safety have been confirmed not only for erectile dysfunction but also in treating other diseases.
Viagra lowers blood pressure by supplying sufficient blood to the peripheral organs of the lungs, using the same principle as in treating erectile dysfunction. Pfizer, the U.S. drugmaker, has approval to sell Viagra as a treatment for pulmonary arterial hypertension under the name Revatio. But Prigione said, "More patients are needed to validate the findings, so people with Leigh syndrome should not take this drug on their own," adding, "If patients or physicians want to use it, we will gladly cooperate."
Cell (2026), DOI: https://doi.org/10.1016/j.cell.2026.02.008