Disease relevance of SC 0735

• Furthermore, where nitisinone is used pre-emptively, liver disease appears to be prevented, suggesting the importance of neonatal screening for tyrosinaemia where possible [1].
• OBJECTIVES: Medical treatment of tyrosinemia I relies on the herbicide NTBC [Orfadin 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione], an inhibitor of plant and mammalian 2-oxoacid-utilizing dioxygenases with a collective catalytic cycle ('HAG' mechanism) [2].
• Use of nitisinone in patients with alkaptonuria [3].
• Nitisinone may be a promising agent in metastatic neuroblastoma [4].
• Successful symptomatic treatment of ochronotic arthropathy with joint replacement has been documented, and a new pharmacotherapeutic agent, nitisinone, is currently under investigation for both prevention and treatment of ochronosis [5].

High impact information on SC 0735

• Nitisinone is indicated for all children with HT-1, and liver transplantation is only indicated where nitisinone fails, or where the development of HCC is likely or suspected [1].
• Although nitisinone can reduce HGA production in humans with homogentisate 1,2-dioxygenase deficiency, the long-term safety and efficacy of this treatment require further evaluation [6].

Chemical compound and disease context of SC 0735

• We investigated the safety and the HGA-depleting efficacy of nitisinone in an open-label, single-center study of 9 alkaptonuria patients (5 women, 4 men; 35-69 years of age) over the course of 3 to 4 months [3].
• Nitisinone blocks the tyrosine pathway and may be effective in treating neuroblastoma [4].

Analytical, diagnostic and therapeutic context of SC 0735

• Future long-term clinical trials are planned to determine the benefits of nitisinone in preventing joint deterioration and providing pain relief, and its long-term side effects [3].

References