- Email: [email protected]
Renal diseases
Drug Discovery Today: Therapeutic Strategies
Vol. 4, No. 1 2007
Editors-in-Chief Raymond Baker – formerly University of Southampton, UK and Merck Sharp & Dohme, UK Eliot Ohlstein – GlaxoSmithKline, USA DRUG DISCOVERY
TODAY THERAPEUTIC
STRATEGIES
Renal diseases
EDITORIAL
Renal diseases Michael S. Goligorsky Renal Research Institute, Medical College, Valhalla, NY, USA. Email: [email protected]
‘Medicine has always been under pressure to provide public explanations for the diseases with which it deals, and the formulation of comprehensive, unifying theories has been the most ancient and willing preoccupation of the profession. In the earliest days, hostile spirits needing exorcism were the principal pathogens, and the shaman’s duty was simply the development of improved techniques for incantation. Later on . . .’ Lewis Thomas, The Medusa and the Snail Modern medicine has witnessed escalating numbers of patients suffering from kidney disease. At the same time, modern health care organizations have experienced an increasing financial burden. In the United States alone, 12 million people (6.5% of the population) have evidence of microalbuminuria and 8 million people or 4.3% of the population exhibit signs of reduced renal function (US Renal Data System). Progression of chronic kidney disease to the endstage requiring dialysis and kidney transplantation afflicts currently nearly 0.5 million people and program expenditures have reached $32 billion. The latest figures from the US Renal Data System 2006 annual report indicate that a staggering 7% of Medicare patients have chronic kidney disease, which accounts for 24% of the insurance’s expenditures. Treatment strategies and therapeutic interventions have been devised to curtail the development and progression of renal disease, but, unfortunately, neither has been successful. Not surprisingly, the search for novel strategies to prevent and rationally treat kidney disease is intense. Translating a mechanistic observation into a rational therapy is arduous. Biomedical research into disease mechanisms provides a stream of observations and discoveries, some of which unveil novel therapeutic targets. These in turn ignite the search for chemicals or biologicals directed at the desired targets. Only a tiny proportion of these eventually overcome stringent analyses of efficacy, toxicity and pharmacokinetics 1740-6773/$ ß 2007 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.ddstr.2007.11.003
to reach the patient in need. As Lewis Thomas wrote in The Medusa and the Snail ‘sometimes there are ten, even twenty different ways to go, all but one bound to be wrong, and the richness of selection in such situations can lift us onto totally new ground’. The general strategic plan outlined above – from pathogenetically rational selection of drug targets to the analysis of the efficacy and safety of various drug candidates – is followed by the eminent contributors to this issue of Drug Discovery Today: Therapeutic Strategies in their pursuit of new therapeutic
Box 1. Section Editor Michael S. Goligorsky Michael S. Goligorsky received his MD and PhD degrees from the Kiev Medical School (1970 and 1973), where he was on the faculty in the Department of Internal Medicine and Institute of Urology and Nephrology until he joined Ben Gurion University Medical School in Beer-Sheba (1980). In 1982 he received a minisabbatical at Yale University Medical School and in 1984 moved to Washington University of St Louis to advance his subspecialty training and research on calcium metabolism in kidney disease. He was among the first to develop fluorescence microscopy approaches to measurements of cytosolic calcium concentration. At the State University of New York (Stony Brook), while growing through the ranks and becoming Professor of Medicine and Physiology, he pursued studies of acute and chronic kidney disease and the mechanisms of developing cardiovascular complications (1988–2002). In 1996 he took a sabbatical leave to advance these subjects at the University College London, where he was named Honorary Professor. Since 2002 he is heading Renal Research Institute at New York Medical College and provides academic leadership in the Division of Nephrology.
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Drug Discovery Today: Therapeutic Strategies | Renal diseases
strategies and pharmaceuticals. Some of these strategies are at early stages of development, others are advanced. The problem of acute renal injury is discussed in the review on endothelial progenitor cells by D. Patschan. Other reviews discuss attempts at halting the progression of renal disease using pharmacological modulation of hypoxia-inducible factor-1 (KU Eckardt’s laboratory) and novel erythropoietin mimetics (G. Gobe and collaborators). Problems of preventing the development and progression of diabetic macrovascular and microvascular complications are addressed in
64
www.drugdiscoverytoday.com
Vol. 4, No. 1 2007
the reviews on advanced glycation end-product breakers by Cooper’s group and the selenoorganic antioxidant/peroxynitrite scavenger, ebselen by Chen and co-workers. This selection of reviews tackles some of the most persistent nephrological problems in the clinic and illustrates the broad-based geography of research conducted in these areas. It is my sincere hope that the reader will gain some insights into the new strategies to tackle kidney diseases and thereby becomes energized in the desire to contribute to these efforts.
Vol. 4, No. 1 2007
Editors-in-Chief Raymond Baker – formerly University of Southampton, UK and Merck Sharp & Dohme, UK Eliot Ohlstein – GlaxoSmithKline, USA DRUG DISCOVERY
TODAY THERAPEUTIC
STRATEGIES
Renal diseases
EDITORIAL
Renal diseases Michael S. Goligorsky Renal Research Institute, Medical College, Valhalla, NY, USA. Email: [email protected]
‘Medicine has always been under pressure to provide public explanations for the diseases with which it deals, and the formulation of comprehensive, unifying theories has been the most ancient and willing preoccupation of the profession. In the earliest days, hostile spirits needing exorcism were the principal pathogens, and the shaman’s duty was simply the development of improved techniques for incantation. Later on . . .’ Lewis Thomas, The Medusa and the Snail Modern medicine has witnessed escalating numbers of patients suffering from kidney disease. At the same time, modern health care organizations have experienced an increasing financial burden. In the United States alone, 12 million people (6.5% of the population) have evidence of microalbuminuria and 8 million people or 4.3% of the population exhibit signs of reduced renal function (US Renal Data System). Progression of chronic kidney disease to the endstage requiring dialysis and kidney transplantation afflicts currently nearly 0.5 million people and program expenditures have reached $32 billion. The latest figures from the US Renal Data System 2006 annual report indicate that a staggering 7% of Medicare patients have chronic kidney disease, which accounts for 24% of the insurance’s expenditures. Treatment strategies and therapeutic interventions have been devised to curtail the development and progression of renal disease, but, unfortunately, neither has been successful. Not surprisingly, the search for novel strategies to prevent and rationally treat kidney disease is intense. Translating a mechanistic observation into a rational therapy is arduous. Biomedical research into disease mechanisms provides a stream of observations and discoveries, some of which unveil novel therapeutic targets. These in turn ignite the search for chemicals or biologicals directed at the desired targets. Only a tiny proportion of these eventually overcome stringent analyses of efficacy, toxicity and pharmacokinetics 1740-6773/$ ß 2007 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.ddstr.2007.11.003
to reach the patient in need. As Lewis Thomas wrote in The Medusa and the Snail ‘sometimes there are ten, even twenty different ways to go, all but one bound to be wrong, and the richness of selection in such situations can lift us onto totally new ground’. The general strategic plan outlined above – from pathogenetically rational selection of drug targets to the analysis of the efficacy and safety of various drug candidates – is followed by the eminent contributors to this issue of Drug Discovery Today: Therapeutic Strategies in their pursuit of new therapeutic
Box 1. Section Editor Michael S. Goligorsky Michael S. Goligorsky received his MD and PhD degrees from the Kiev Medical School (1970 and 1973), where he was on the faculty in the Department of Internal Medicine and Institute of Urology and Nephrology until he joined Ben Gurion University Medical School in Beer-Sheba (1980). In 1982 he received a minisabbatical at Yale University Medical School and in 1984 moved to Washington University of St Louis to advance his subspecialty training and research on calcium metabolism in kidney disease. He was among the first to develop fluorescence microscopy approaches to measurements of cytosolic calcium concentration. At the State University of New York (Stony Brook), while growing through the ranks and becoming Professor of Medicine and Physiology, he pursued studies of acute and chronic kidney disease and the mechanisms of developing cardiovascular complications (1988–2002). In 1996 he took a sabbatical leave to advance these subjects at the University College London, where he was named Honorary Professor. Since 2002 he is heading Renal Research Institute at New York Medical College and provides academic leadership in the Division of Nephrology.
63
Drug Discovery Today: Therapeutic Strategies | Renal diseases
strategies and pharmaceuticals. Some of these strategies are at early stages of development, others are advanced. The problem of acute renal injury is discussed in the review on endothelial progenitor cells by D. Patschan. Other reviews discuss attempts at halting the progression of renal disease using pharmacological modulation of hypoxia-inducible factor-1 (KU Eckardt’s laboratory) and novel erythropoietin mimetics (G. Gobe and collaborators). Problems of preventing the development and progression of diabetic macrovascular and microvascular complications are addressed in
64
www.drugdiscoverytoday.com
Vol. 4, No. 1 2007
the reviews on advanced glycation end-product breakers by Cooper’s group and the selenoorganic antioxidant/peroxynitrite scavenger, ebselen by Chen and co-workers. This selection of reviews tackles some of the most persistent nephrological problems in the clinic and illustrates the broad-based geography of research conducted in these areas. It is my sincere hope that the reader will gain some insights into the new strategies to tackle kidney diseases and thereby becomes energized in the desire to contribute to these efforts.