THE HISTORY OF DEFERIPRONE (L1) AND THE COMPLETE TREATMENT OF IRON OVERLOAD IN THALASSAEMIA

Abstract

Deferiprone (L1) was originally designed, synthesised and screened in vitro and in vivo in 1981 by Kontoghiorghes G J following his discovery of the novel alpha-ketohydroxypyridine class of iron chelators (1978-1981), which were intended for clinical use. The journey through the years for the treatment of thalassaemia with L1 has been a very difficult one with intriguing turn of events, which continue until today. Despite many complications, such as the wide use of L1 suboptimal dose protocols, the aim of chelation therapy- namely the complete removal of excess iron in thalassaemia major patients, has been achieved following the introduction of specific L1 and L1/deferoxamine combinations. Many such patients continue to maintain normal iron stores. As a result of the introduction of L1, thalassaemia has changed from a fatal to a chronic disease and thalassaemia patients are active professional members in all sectors of society, have their own families with children and grandchildren and their lifespan is approaching that of normal individuals. No changes in the low toxicity profile of L1 have been observed in more than 30 years of clinical use. Thousands of thalassaemia patients are still denied the cardioprotective and other beneficial effects of L1 therapy. The safety of L1 in thalassaemia and other non-iron loaded diseases resulted in its selection as one of the leading therapeutics for the treatment of Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration and other similar cases. There are also increasing prospects for the application of L1 as a main, alternative or adjuvant therapy in many pathological conditions including cancer, infectious diseases and as a general antioxidant for diseases related to free radical pathology.