Leggi in italiano
Scientist preparing samples for automated DNA analysis in a lab. Credit: Tek Image/ SPL/ Getty Images.
One newborn in a million inherits a defective gene behind a deadly condition named Crigler-Najjar Syndrome. It is caused by a total lack of total of an enzyme needed by the liver to eliminate bilirubin, a waste product of the breakdown of ageing red blood cells. In people who don’t have the enzyme, called UDP Glucuronosyltransferase 1A1, the liver cannot clear bilirubin, that builds up in the blood causing jaundice and eventually leading to brain damage and death.
To avoid the progression of the disease, these patients need to be exposed for more than six hours per day to specific light waves that break down the molecule through the skin, and the only real cure is a liver transplant.
A European research consortium led by Lorenzo D’Antiga, at Papa Giovanni XXIII Hospital in Bergamo, treated five patients with a single intravenous infusion of viral vectors delivering a functional copy of the gene to defective liver cells. “The corrective gene is not integrated into chromosomes of the target cell, but works side by side with them, thus preventing the risk of accidentally inducing a malignant mutation,” D’Antiga explains.
The results of the trial appeared in the New England Journal of Medicine1. No serious adverse events were reported. Two patients received a lower dose of the recombinant viruses and showed a temporary decrease in bilirubin concentration. Three received a higher dose, suspended phototherapy 16 weeks after the infusion and still showed non-toxic level of bilirubin 80 weeks after the infusion. “This approach has the potential to be a life-changing breakthrough for Crigler-Najjar patients, sparing them the risks and consequences of liver transplant. It could as well be applied to other genetic liver conditions,” D’Antiga says. “We are now looking for funding to expand the trial.”
