Alkaptonuria (AKU) is a rare autosomal recessive disease caused by a malfunction of the enzyme homogentisate 1,2 dioxygenase (HGD). In January 2019, the DevelopAKUre (FP7 EC) project ended, which included a SONIA2 clinical trial to test the efficacy and safety of nitisinone in the treatment of this disease. Compared to control group of patients with no treatment, in the nitisinone group already at 12 months, u-HGA24 was significantly decreased by 99.7 %, and at 48 months, the significantly lower increase in cAKUSSI score from baseline was observed.
Results indicate that nitisinone slows down the disease progression. Based on the results of the study, the manufacturer of the medicine, SOBI (Swedish Orphan BIovitrum), asked the European Medicines Agency (EMA) for authorization to use the medicine for AKU. The Committee for Medicinal Products for Human Use (CHMP) of EMA has adopted a positive opinion for Orfadin® (nitisinone) for the treatment of adult patients with AKU. The opinion has been now referred to the European Commission for a decision. Two institutions from Slovakia actively participated in: Department of Human Genetics ÚKTV, BMC SAV in Bratislava and NÚRCH in Piestany. Since Slovakia has a primate in AKU – having the highest number of AKU patients worldwide – approximately 200, we offer readers an overview of the latest knowledge about the pathophysiology of this disease, to which the DevelopAKUre project had also contributed.
Key words: alkaptonuria, HGD gene, metabolic disorder, treatment of rare diseases, nitisinone.
Lek Obz, 2020, 70 (1): 33-40
Andrea ZAŤKOVÁ 1, Helena GLASOVÁ 1,2, Richard IMRICH 1,3
1 Ústav klinického a translačného výskumu, Biomedicínske centrum SAV, Dúbravská cesta, Bratislava, riaditeľka prof. RNDr. S. Pastoreková, DrSc.
2 Katedra klinickej farmakológie, Lekárska fakulta Slovenská zdravotnícka Univerzita v Bratislave, prednosta prof. MUDr. J. Glasa, PhD.
3 Národný ústav reumatických chorôb, Nábr. I. Krasku, Piešťany, riaditeľ doc. MUDr. R. Imrich, DrSc.
CITE:
ZAŤKOVÁ A., GLASOVÁ H., IMRICH R.: Advances in research of alkaptonuria and its potential treatment. Lek Obz, 2020, 70 (1): 33-40
