Advances in iron overload therapies. prospects for effective use of deferiprone (L1), deferoxamine, the new experimental chelators ICL670, GT56-252, L1NA11 and their combinations.
Effective new therapies and mechanisms have been developed for the targeting and prevention of iron overload and toxicity in thalassaemia and idiopathic haemochromatosis patients. A new era in the development of chelating drugs began with the introduction of deferiprone or L1, which as a monotherapy or in combination with deferoxamine can be used universally for effective chelation treatments, rapid iron removal, maintenance of low iron stores and prevention of heart and other organ damage caused by iron overload. Several experimental iron chelators such as deferasirox (4-[3,5-bis (2-hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid) or ICL670, deferitrin (4,5-dihydro-2- (2,4-dihydroxyphenyl)-4-methylthiazole-4 (S)-carboxylic acid) or GT56-252, 1-allyl-2-methyl-3-hydroxypyrid-4-one or L1NAll and starch deferoxamine polymers have reached different stages of clinical development. The lipophilic ICL670, which can only be administered once daily is generally ineffective in causing negative iron balance but is effective in reducing liver iron. It is suspected that it may increase iron absorption and the redistribution of iron from the liver to the heart and other organs. The experimental iron chelators do not appear to have significant advantages in efficacy and toxicity by comparison to deferiprone, deferoxamine or their combination. However, the prospect of combination therapies using deferiprone, deferoxamine and new chelators will provide new mechanisms of chelator interactions, which may lead to higher efficacy and lower toxicity by comparison to monotherapies. A major disadvantage of the experimental chelators is that even if they are approved for clinical use, they are unlikely to be as inexpensive as deferiprone and become available to the vast majority of thalassaemia patients, who live in developing countries.
Kontoghiorghes
George J
GJ
Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3 Ammochostou Street, Limassol 3021, Cyprus. pri_gjk@cylink.com.cy
Eracleous
Eleni
E
Economides
Charalambos
C
Kolnagou
Annita
A
D001565:Benzoates / Q000627:therapeutic use; D002264:Carboxylic Acids / Q000627:therapeutic use; D000077588:Deferasirox; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006432:Hemochromatosis / Q000188:drug therapy; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy*; D011728:Pyridones / Q000627:therapeutic use; D017262:Siderophores / Q000627:therapeutic use; D013789:Thalassemia / Q000188:drug therapy; D013844:Thiazoles / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
C507647:1-allyl-2-methyl-3-hydroxypyrid-4-one; C120073:4'-hydroxydesazadesferrithiocin; D001565:Benzoates; D002264:Carboxylic Acids; D007502:Iron Chelating Agents; D011728:Pyridones; D017262:Siderophores; D013844:Thiazoles; D014230:Triazoles; D000077543:Deferiprone; D003676:Deferoxamine; D000077588:Deferasirox