The process of drug discovery to combat human disease is often long and tortuous. Most often the successful development of a therapy relies, first, on the identification of a drug target and, second, on the development of agents, which can manipulate that target to reverse or arrest the course of disease. Drug targets are commonly critical elements of the pathologic process, which can be manipulated without seriously affecting normal human function.
In the modern world, the identification of drug targets requires a thorough understanding of the molecular mechanisms of disease and the identification of novel therapies. Needless to say, this process is not always fruitful. It has been reported that as many as 95 percent of the drugs in development are ultimately rejected because they lack clinical efficacy or have unacceptable side effects (1). This has recently led to a number of expensive failures of drugs in phase three clinical trials, which can each cost as much as 1 billion dollars (US). Hence, there is a great need for a more efficient process of drug discovery.
To address this issue the United States National Institutes of Health, ten pharmaceutical companies and seven non-profit disease-oriented advocacy groups have joined together to form the “Accelerating Medicines Partnership (AMP)” to identify novel drug targets. Initially, this pilot program will focus on four human diseases: Alzheimer’s disease, type 2 diabetes and the autoimmune disorders: rheumatoid arthritis and systemic lupus erythematosus (2). However, according to Dr. Francis Collins, the Director of the NIH “These three-to-five year pilot projects will set the stage for broadening AMP to other diseases and conditions.” (3)
The initiative will strive to use modern genetic and biochemical approaches to: 1) shorten the development time that is needed to identify targets, 2 ) improve the prospect that manipulation of the target will result in the development of a valid therapy for disease and 3) lower the cost of the whole process. Both the public and private organizations will contribute equally to the cost of the project and each will contribute scientists with expertise in the targeted disease areas. Most importantly, the results of discoveries from the project will be freely available to all.
An example of the kind of discoveries that the program hopes to make is the identification of the molecular mechanisms that underlie spontaneous genetic mutations (so called experiments of nature) that result in individuals with significant resistance to human disease. In our own field this approach is similar to the identification of the molecular mechanisms of sclerosteosis and Van Buchan’s disease (4), which produce individuals with a high bone mass phenotypes because they lack sclerostin. This protein is now the target of a potential therapy for osteoporosis, which is in clinical trials and is based on the development of neutralizing antibodies to sclerostin.
Currently, the AMP is in its infancy and it remains to be seen whether its approach is a viable one given the competitive pressures of the pharmaceutical industry. However, it represents a significant new approach to drug discovery that, if successful, has the potential to have major affects on this process for years to come.
Farmington, CT, USA
A Public-Private Partnership for Drug Discovery
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