to the discovery of a therapeutic approach. Imatinib mesylate (Gleevec), the drug discovered by Druker, specifically deactivates the enzyme target in CML. It was approved by the Food and Drug Administration (FDA) in 2001 and is now used not only for CML but also for other rare cancers. Increased knowledge of kinase inhibitors (of which imatinib was the first) is supporting the development of more potent, second-generation drugs for CML that may also be less susceptible to resistance (Sawyers, 2010).
Today, as a result of scientific and technological innovations, much of the basic research initially undertaken with CML could be done more quickly, inexpensively, and easily. For example, identification of the genetic cause of conditions that are clearly inherited used to involve speculative approaches and laborious analytical tools. The sequencing of the human genome has spawned an array of rapid and relatively inexpensive DNA analysis tools that have the potential to foster more targeted and efficient therapeutics development for rare diseases. Advances in the scientific understanding of disease mechanisms likewise are helping researchers focus more efficiently and effectively on potential therapeutic targets. As a result, the future holds the promise of continued innovation that will further accelerate biomedical research to the benefit of patients with rare as well as common diseases.
As discussed in Chapter 1, research on rare diseases can illuminate disease mechanisms and therapeutic opportunities for more common diseases. Box 4-1 briefly summarizes several additional examples of rare diseases research that have yielded broader knowledge.
Many of the same approaches and techniques are used to study both rare and common diseases, but research on rare diseases faces some special barriers and constraints. One is the sheer number of rare diseases, an estimated 5,000 to 8,000. Many of the challenges stem from the low prevalence that is the defining characteristic of rare diseases. Particularly for extremely rare conditions, the small numbers of affected individuals means a dearth of biological specimens, which severely limits studies of disease mechanism and etiology. Small numbers also constrain epidemiologic research and clinical trials as highlighted in Chapters 3 and 5. Other challenges include the limited funding for research and a limited number of investigators committed to the study of rare conditions.
The basic research tools available to investigators have advanced dramatically over the past 20 years, with new approaches continuing to evolve, both in the laboratory and from the use of computational biology. Along with new and better tools, models for supporting discovery research have also undergone a transformation in recent years. This chapter briefly examines the implications for rare diseases research of a number of current research strategies for both target discovery and therapeutic discovery. The next chapter focuses on product development, particularly from the perspective of companies and their academic and government collaborators