Current treatments include daily phototherapy and liver transplantation.
Crigler–Najjar syndrome, a rare genetic disorder characterized by the absence of the enzyme UGT1A1, leads to severe jaundice and can be fatal. A recent phase 1–2 study has explored the potential of gene therapy using an adeno-associated virus vector encoding UGT1A1, offering a new therapeutic avenue for patients with this challenging condition.
- Study Design
- Phase 1–2 dose-escalation study
- Five patients with Crigler–Najjar syndrome treated with phototherapy
- Single intravenous infusion of adeno-associated virus serotype 8 vector encoding UGT1A1 (GNT0003)
- Two patients received 2×10¹² vg/kg, three received 5×10¹² vg/kg
- Primary end points: safety and efficacy, with efficacy defined by serum bilirubin level of 300 μmol per liter or lower at 17 weeks
- Key Findings
- No serious adverse events reported
- Common adverse events: headache, alterations in liver-enzyme levels
- Alanine aminotransferase increased in four patients, treated with glucocorticoids
- Lower dose exceeded 300 μmol per liter bilirubin; higher dose led to levels below 300 μmol per liter without phototherapy (mean level at final follow-up: 149±33 μmol per liter)
- Gene therapy with GNT0003 was safe in this small study
- Higher dose resulted in decreased bilirubin levels, with patients not receiving phototherapy at least 78 weeks after vector administration.
Did You Know?
Crigler–Najjar syndrome is so rare that it affects approximately 1 in a million newborns, making traditional treatments like liver transplantation challenging.