A compound found in Viagra may offer unexpected hope for those battling Leigh syndrome, a rare and often fatal genetic disorder that typically manifests before a child’s second birthday. This discovery, published in the journal Cell, highlights a potential fresh avenue for treating this devastating condition.
Researchers have found that sildenafil, the active ingredient in Viagra, corrected certain abnormalities in cells carrying genetic variations linked to Leigh syndrome during pre-clinical trials. The compound also modestly extended the lifespan of rodents and pigs with other mutations associated with the syndrome.
Preliminary results also suggest sildenafil may alleviate symptoms in some patients. In one case, a 16-year-old whose condition was rapidly deteriorating and who was being considered for palliative care saw improvements in his symptoms seven years after beginning treatment, though he still requires assistance to walk.
“They saw improvement in several characteristics, so it’s very encouraging, but there’s still a lot to measure,” said Dr. Grant Mitchell, a geneticist at CHU Sainte-Justine, a hospital in Montreal.
Leigh syndrome is a severe and currently incurable form of mitochondrial disease, causing psychomotor regression and metabolic crises. Mitochondrial diseases are a group of inherited disorders that affect the function of mitochondria, which are responsible for creating energy from the food we eat. These disorders can have a significant impact on overall health and development.
Children with Leigh syndrome often develop difficulties with breathing and swallowing, though symptoms can sometimes appear later in adolescence or adulthood. The syndrome can be caused by defects in multiple genes, according to Dr. Mitchell.
“There are multiple forms of Leigh syndrome, and it’s not certain that all forms would respond in the same way to treatment with sildenafil,” he said. “There is one form of the syndrome that is more common in Quebec than elsewhere due to a historical genetic founder effect. Neither this form, nor the responsible gene, were mentioned in the published study.”
Previous research identified an abnormal electrical charge in the membranes of mitochondria linked to the MT-ATP6 gene. In the new study, researchers screened nearly 6,000 molecules and found sildenafil particularly effective in restoring a normal electrical charge.
Further laboratory and animal testing confirmed the molecule’s potential to correct some of the problems associated with the disease. Six patients were prescribed sildenafil as part of the research. One patient had to discontinue treatment due to side effects, but four others experienced modest improvements.
“The way the drug produced the effects remains speculative,” Dr. Mitchell noted. “The drug is known to dilate blood vessels, but there may be other effects. It’s not clear by what pathway taking sildenafil is linked to the beneficial effects. But the effects are very encouraging.”
Researchers caution that the study was limited in scope and duration, and that it focused on a single form of the disease. Experts also point out that Leigh syndrome can be episodic, with symptoms fluctuating, making it difficult to isolate the drug’s effect from the natural progression of the illness.
“It was over a short period, it was analyzed with only one form of the disease, and we cannot develop into too optimistic, but if everything continues to travel like this…,” Dr. Mitchell said. “The authors have taken a sizeable step forward; it’s a very complex and detailed paper.”
Researchers A. Prigione and M. Schuelke have filed patent applications for sildenafil in the treatment of CIV and CV defects and obtained Orphan Drug Designation from the European Medicines Agency for sildenafil in Leigh syndrome.
