For the first time, research led by Associate Professor Duc Dong, Ph.D., demonstrated that a drug can stimulate liver regeneration in Alagille syndrome.
Alagille syndrome is caused by a mutation that prevents the formation and regeneration of bile ducts in the liver. It affects over 4,000 babies each year. The patients frequently require a liver transplant, but donor’s livers are limited, and not all children qualify. In addition, the disease kills 75% of children by late adolescence without transplant. A genetic mutation causes a decrease in Notch signaling in children with this dangerous condition. Moreover, this results in poor liver duct growth and regeneration.
According to this research, activating the Notch pathway with a medication may be sufficient to restore the liver‘s natural capacity for regeneration.
“Alagille syndrome is widely considered an incurable disease, but we believe we’re on the way to changing that,” says Dong, the associate dean of admissions for Sanford Burnham Prebys’ graduate school.
NoRA1 and dealing with Alagille syndrome:
The study was published in the proceedings of the National Academy of Sciences. It has the potential to transform treatment for this rare disease and may have implications for more common diseases as well.
Because of impaired Notch signalling, most children with this illness do not experience the liver’s exceptional capacity for regeneration. The exciting study gives families who are dealing with this extremely difficult condition hope.
NoRA1 activates the Notch pathway, a cell-to-cell signaling system found in nearly all animals. Notch signaling aids in the management of basic biological processes and is involved in a variety of diseases. The researchers discovered that in animals with mutations in the same gene that causes the disease.
Also, NoRA1 increases Notch signaling and causes duct cells in the liver to regenerate and repopulate, reversing liver damage and increasing survival.
Future of the treatment :
The drug is currently being tested on miniature livers cultured in the lab with stem cells derived from patients’ cells.
Dong is also forming a start-up company to move this drug into clinical trials. The new company’s initial focus will be on this particular illness. Moreover it also intends to develop this drug for other, more common diseases, such as certain cancers.