Feautured pharmaceutical scientist
Professor Bob Hider
Emeritus Professor of Medicinal Chemistry, King’s College London
Although iron is essential for life, excess iron is toxic as it generates free radicals which damage biological tissue. Toxic iron levels can occur in man as a result of regular blood transfusion, which is essential treatment for patients suffering from inherited diseases, such as thalassaemia and sickle cell anaemia. Professor Bob Hider, Emeritus Professor of Medicinal Chemistry at King’s College London, is involved in the design and development of orally active iron chelators for the removal of toxic iron.
Originally Bob Hider trained in Chemistry at King’s College London, gaining his PhD in 1967. Following a 3 year research fellowship at St Thomas’ Hospital in London, Bob moved to Essex University where his research centred on iron uptake processes in micro-organisms, plants and mammalian cells. This work led to the development of a range of novel orally active iron chelators for the treatment of iron overload. One of these compounds, deferiprone, has been licensed in Europe and the United States and is available in the UK for the treatment of iron overload in patients with thalassaemia major. Thalassaemia is the most prevalent inherited single-gene disorder in the world. Life saving therapy involves regular blood transfusions which result in iron accumulation in the body, leading to potentially fatal cardiac iron burden. To counter such iron accumulation, iron chelation therapy is required. Prior to the discovery of deferiprone, iron chelation involved administration of desferrioxamine by continuous infusion over six to eight hour periods, typically five times a week. The duration and frequency of the administration led to poor adherence with many patients. The introduction of the orally active, deferiprone has resulted in significant benefits for patients in terms of ease of administration and improved quality of life. Furthermore, by virtue of reduced costs, it has rendered iron chelation therapy available to patients in the third world.
A key property of deferiprone is its ability to remove iron from the heart, thereby reducing the incidence of myocardial dysfunction in iron-overload patients. Myocardial infarction was a major cause of death with desferrioxamine-treated patients, but with deferiprone this serious pathology is avoided. Since deferiprone’s introduction, Bob and his team have continued to develop orally active iron chelators with the aim of designing more potent, less toxic analogues. This has led to the development of more effective second generation iron chelators, two of which are currently being investigated in related clinical trials. In order to facilitate the monitoring of patients receiving iron chelation therapy Bob Hider’s research group has introduced two new clinical tests; the measurement of so called “non-transferrin bound iron” (NTBI), a toxic form of iron that can appear in the blood and the quantification of hepcidin, a recently discovered hormone which controls body iron levels.
Over the past decade it has become apparent that elevated iron levels in certain brain regions can lead to neurodegeneration, being particularly marked in Friedreich’s ataxia and Parkinson’s disease. Significantly the only clinically approved iron chelator which can cross the blood brain barrier is deferiprone. Consequently deferiprone is currently involved in several international clinical trials, which are centred on these two diseases. With both diseases there has been appreciable improvement in the deferiprone treated patients. The Hider group is currently designing and investigating deferiprone analogues which penetrate the brain more effectively.
In the course of his career, Bob has published over 350 refereed publications, been granted 21 patents and supervised 75 PhD students. His work was recently recognized through the presentation of the Royal Pharmaceutical Society’s Hanbury Memorial Award in 2014.