The role of nitisinone in tyrosine pathway disorders

Curr Rheumatol Rep. 2014 Nov;16(11):457. doi: 10.1007/s11926-014-0457-0.

Abstract

Nitisinone 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC), an effective herbicide, is the licensed treatment for the human condition, hereditary tyrosinaemia type 1 (HT-1). Its mode of action interrupts tyrosine metabolism through inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD). Nitisinone is a remarkable safe drug to use with few side effects reported. Therefore, we propose that it should be investigated as a potential treatment for other disorders of tyrosine metabolism. These include alkaptonuria (AKU), a rare disease resulting is severe, early-onset osteoarthritis. We present a case study from the disease, and attempts to use the drug both off-label and in clinical research through the DevelopAKUre consortium.

Publication types

  • Review

MeSH terms

  • 4-Hydroxyphenylpyruvate Dioxygenase / antagonists & inhibitors
  • Alkaptonuria / drug therapy*
  • Animals
  • Biomedical Research
  • Cyclohexanones / therapeutic use*
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Nitrobenzoates / therapeutic use*
  • Off-Label Use
  • Tyrosinemias / drug therapy*

Substances

  • Cyclohexanones
  • Enzyme Inhibitors
  • Nitrobenzoates
  • 4-Hydroxyphenylpyruvate Dioxygenase
  • nitisinone