Treatment for Alagille syndrome, a rare genetic disorder that affects multiple organ systems, are typically symptomatic. Many children born with this disorder eventually require a liver transplant; without this, Alagille syndrome can be fatal. As a result, many scientists are searching for new and effective treatment options to mitigate organ damage and improve patient outcomes. According to a report in Science Alert, scientists recently identified NoRA1 as a potential therapeutic intervention.
In Alagille syndrome, the genetic mutations reduce signaling in the Notch pathway, which plays a role in different biological systems. For example, the Notch pathway plays a role in liver health and maintenance. So reduced signaling causes poor bile duct growth, poor liver regeneration, and bile accumulation. NoRA1 targets this pathway to optimize treatment.
Scientists recently explored the efficacy of NoRA1 in zebrafish models. The findings, published in PNAS, show that NoRA1 helped improve Notch signaling. This contributed to healthy liver tissue regeneration. Scientists found that even a single NoRA1 dose contributed to a threefold improvement in overall survival rates. More so, NoRA1 targets the natural processes within the body to assist with regeneration.
Currently, the research team has expanded its focus to liver organoids. More research is needed to understand the impact of NoRA1 and to determine if it truly could be a treatment option in the future.
What is Alagille Syndrome?
JAG1 and NOTCH2 gene mutations have been implicated in the development of Alagille syndrome. While Alagille syndrome affects multiple organ systems, the impact and affected systems vary from person to person. Liver disease and heart abnormalities are common in patients. Symptoms, which typically manifest within the first three months of life, can include:
- Jaundice (yellowing of the skin, eyes, and mucous membranes)
- Failure to thrive
- Poor weight gain
- Reduced number of bile ducts
- Pulmonic stenosis
- Impaired blood flow from the heart to the lungs
- Severe itchiness
- Cholestasis (blocked bile flow from the liver)
- Heart murmurs
- Deeply-set and widely-spaced eyes, a pointed chin, and a broad forehead
- Spine growth changes
- Pale, loose stools
- Hard skin bumps