New and promising treatment for “incurable” fatal syndrome!

Alagille syndrome is known as a fatal genetic disease that affects various organs and systems, primarily the liver. There is currently no known cure for it, but scientists have now identified a potentially effective treatment.

The newly developed drug, called NoRA1, targets the Notch pathway, a cellular-level signaling system in the body that is important for many vital biological systems, including proper liver maintenance.

The genetic mutation behind Alagille syndrome causes reduced Notch signaling, which then leads to impaired growth and regeneration of the bile ducts, causing bile buildup and liver damage.

Zebrafish are often used in human disease research due to our extensive knowledge of their genome, gene similarities, and the ease with which their evolution can be observed. In the most recent studies, NoRA1 has been shown to enhance Notch signaling in zebrafish with gene mutations similar to those found in children diagnosed with the disease.

The duct cells were stimulated to grow and regenerate, as healthy liver tissue does, reversing liver damage in zebrafish. The survival chances of the zebrafish participating in the study were increased by the application of the treatment. In fact, just one dose of NoRA1 four days after fertilization was enough to achieve a three-fold improvement in survival rates.

“The liver is known for its excellent ability to regenerate, but most children with Alagille syndrome don’t do that because of impaired Notch signaling,” says molecular biologist Chengjian Zhao of Stanford’s Burnham Prebis Medical Discovery Institute in California. that converting the Notch pathway into drug A may be enough to restore the liver’s natural ability to regenerate.”

One of the advantages of the drug is that it targets the processes in the body that should occur naturally. This bodes well when it comes to testing this on real people in the future if the treatment moves into clinical trials.

“Instead of forcing cells to do something extraordinary, we simply encourage the natural process of regeneration, so I am optimistic that this will be an effective treatment for Alagille syndrome,” says molecular biologist Duke Dong of Stanford Burnham. Prebis Medical Discovery Institute.

NoRA1 can help with other common diseases as well, and is critical to the Notch pathway for the proper functioning of daily biological processes. However, the focus now is on how to help treat this rare liver disease.

More than 4,000 children are born with Alagille syndrome each year, and a liver transplant is often required. Without transplants and lack of donors, the mortality rate in late adolescence is 75%.

The researchers are currently working on lab-grown mini-livers using stem cells obtained from patients with Alagille syndrome to further test the NoRA1 drug.

The study is published in PNAS.

Source: Science Alert