Vol 8, No 3 - Drug Discovery and Proof of Concept
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he discovery and development of one new drug costs around $800 million (taking failures into account) and takes an average of 10 to 12 years. This degree of investment, with such a late return on this investment, is unparalleled in human activity. Despite this investment, some areas of great therapeutic need do not have optimal treatments—acute stroke and Alzheimer’s disease, as well as other central nervous sys- tem (CNS) disorders. There are no drugs registered for the treatment of acute stroke, which is an area of great therapeutic need, being the third-highest cause of mor- tality  and  the  second-highest  cause  of  morbidity. Nevertheless, there are distinct methodological reasons in the clinical trials which can preclude demonstrating efficacy in stroke under many circumstances.1 Another area in which the pharmaceutical industry has failed to revolutionize  therapy  has  been  in  the  treatment  of Alzheimer’s disease. However, preventive therapy by addressing hypertension using angiotensin-converting enzyme  inhibitors  (perindopril, in  the  PROGRESS study) has shown marked reduction in the incidence of stroke, and  also  of  dementia  and  cognitive  decline.2,3 Antidepressant drugs with higher efficacy and fewer side effects are much needed. Effective drug discovery requires drug targets for ther- apeutic intervention which are pivotal points for the dis- ease  process, and  up  until  now  these  have  not  been clearly identified for stroke (with the possible exception of tissue plasminogen activator for very early interven- tion) or Alzheimer’s disease. Background Only 35 new compounds were registered with the Food and  Drug  Administration  (FDA)  in  2003  despite  a research expenditure by the major pharmaceutical firms P h a r m a c o l o g i c a l  a s p e c t s T Copyright © 2006 LLS SAS.  All rights reserved www.dialogues-cns.org New directions for drug discovery Michael Spedding, PhD Keywords: drug discovery; pathophysiology; drug testing; screening Author  affiliations: Deputy Research Director, Chairman NC-IUPHAR, Experimental Sciences, Servier Research Institute, Suresnes, France Address for correspondence: Prof  Michael Spedding, Deputy Research Director, Chairman NC-IUPHAR, Experimental Sciences, Servier Research
Institute, des 11 Rue Moulineaux, 92150 Suresnes, France (e-mail: michael.spedding@fr.netgrs.com) Modern drug discovery demands an integrative approach, using many different technologies, but ultimately based on an understanding of the pathophysiology of the dis- ease state to be treated. Targeting drugs at the main pathophysiological process is the key to success. This issue needs to be addressed with the multiple screening systems available, which can be used to find new leads. © 2006, LLS SAS Dialogues Clin Neurosci. 2006;8:295-301.