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Treatment of Alkaptonuria and Tyrosinemia type 1

Alkaptonuria treatmentIncreased 4-HPPD inhibitionLower tirosinemiaTechShareDay-d1w3Type 1 tyrosinemia treatment


The invention relates to triketones compounds for their use in the prevention and treatment of a disease characterized by accumulation of homogentisic acid (HGA) or succinyl acetoacetate and succinylacetone. The invention also relates to compositions comprising such compounds.

Technical features

Alkaptonuria (AKU) is a rare genetic disease caused by an accumulation and oxydation of homogentisic acid (HGA) due to insufficient activity of homogentisate 1,2-dioxygenase (HGD) involved in tyrosine catabolism. The herbicide nitisinone (compound 1) is a potent inhibitor of both human and rat 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) which catalyses the transformation of the 4-hydroxyphenylpyruvate (HPP) to HGA. Approved by the FDA “in exceptional circumstances” as a life-saver in the rare paediatric hereditary disease tyrosinemia type 1 (HT1), the use of compound 1 is linked to severe side effects. Recent clinical trials confirmed that compound 1 consistently reduces HGA levels in both plasma and urine, albeit correlated with tyrosine accumulation in plasma. Alternative 4-HPPD inhibitors for AKU and HT1 treatment that reduce HGA accumulation while minimizing tyrosinemia are therefore needed.

Possible Applications

  • Rare genetic diseases;
  • Novel treatment of alkaptonuria;
  • Novel treatment of type 1 tyrosinemia;
  • Pharmaceutical composition.


  • Novel alternative nitisinone (NTBC) compounds;
  • Increased 4-HPPD inhibition;
  • Lower cytotoxicity.