Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The introduction of oral chelation therapy with the alpha-ketohydroxypyridine chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1, INN/BAN: deferiprone) in iron- and aluminium-overloaded patients has been initiated in over 15 countries in the last 7 years. Over 600 patients with various conditions, in 26 centres have received L1, in some cases daily for over 5 years. In the vast majority of iron-loaded patients, doses of 55-100 mg kg-1 of L1 resulted in urinary iron excretion levels greater than those accumulating from transfusions (15-35 mg d-1) and also reduction in serum ferritin and liver iron to near normal levels. Urinary iron excretion was related to the iron load of the patients, as well as the dose and frequency of administration of L1. The L1 appears to mobilize iron mainly from a serum iron pool in excess of transferrin saturation, transferrin-bound iron and tissue iron, mainly but not exclusively from the liver. The order of metal binding by L1 at pH 7.4 is Fe > Cu > A1 > Zn. Aluminium removal from aluminium-loaded renal dialysis patients by L1 was also effective at doses similar to those used for iron-loaded patients. Overall toxic side effects include six cases of reversible agranulocytosis, 0-30% incidence of transient musculoskeletal and joint pains, 0-6% of gastric intolerance and 0-2% zinc deficiency. Deferiprone appears to be as effective as desferrioxamine in iron and aluminium removal and has low toxicity. Its oral efficacy and low cost make it more accessible than desferrioxamine for the vast majority of patients needing iron chelation worldwide. The development of other alpha-ketohydroxypyridines is currently in progress.
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PMID:New concepts of iron and aluminium chelation therapy with oral L1 (deferiprone) and other chelators. A review. 774 Dec 39

In the last few years we have witnessed the emergence of oral chelation which is a new form of therapy for transfusional iron-loaded patients in thalassaemia and other refractory anaemias. The need for a cheap, non-toxic, orally effective iron chelator is paramount because it could potentially save the lives of many thousands of patients. At present, less than 10% of the patients requiring iron chelation therapy worldwide receive the widely used chelating drug desferrioxamine (DF) because of its high cost, oral inactivity and toxicity. The most promising oral iron chelator is 1, 2-dimethyl-3-hydroxypyrid-4-one (L1 or INN: Deferiprone), which has so far been taken by over 450 patients in 15 countries, and in some cases daily for over 4 years with very promising results. L1 was shown at 50-100 mg/kg/day to be effective in bringing patients to negative iron balance. It increases urinary iron excretion, decreases serum ferritin levels and reduces liver iron in multi-transfused iron-loaded patients. Toxic side effects were mainly encountered at high doses (80-100 mg/kg/day) and include transient agranulocytosis (5 cases), transient musculoskeletal and joint pains (10-20%), gastric intolerance (2-6%) and zinc deficiency (1%). The incidence of these toxic side effects was reduced by using lower doses of 50-75 mg/kg/day. The overall efficacy and toxicity of L1 is comparable to that of DF in animals and humans. Further work is required for identifying susceptible individuals to L1 toxicity, and also optimum dose protocols of L1 which can maximise iron excretion and minimise the incidence of toxic side effects.
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PMID:Present status and future prospects of oral iron chelation therapy in thalassaemia and other diseases. 826 86