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Innovations in the ability to probe and better understand biologic systems during the past 30 years1-3 have enabled the medical community to develop new therapeutic agents and change the course of many life-shortening diseases. 4, 5 Regardless of this success, bridging the gap between promising laboratory observations and the development of effective therapies remains risky and expensive, with fewer than 1 in 10, 1000 early translational programs efficiently reaching Fda (FDA) approval, at a cost of practically $1 billion. 6 The majority of therapeutic development fails in the preclinical phase, which is sometimes described as the "valley of loss of life. "7
For this reason and because therapies for some conditions will have a restricted eventual market value, the pharmaceutical industry has been hesitant to initiate early-stage programs to treat so-called orphan diseases. In recognition of a critical need, federal firms have developed programs to catalyze innovation and minimize barriers to early development of new therapies. 8 During the past two decades, disease-focused foundations also provide developed a new approach to bridging this preclinical gap. Within a process known as venture philanthropy, such foundations have formed partnerships with industry and federal agencies to talk about the financial risk of therapeutic development, shorten the early translational pipeline, and advance research with "a concentrate on human being, not financial, return. "9 In addition, foundations and their academic partners have accelerated early development by providing access to patient populations for clinical studies and assistance from disease-specific experts in study design, which has helped in bridging the gap in therapeutic development.
With this review, we will concentrate on 3 diseases -- cystic fibrosis, multiple myeloma, and type 1 diabetes mellitus -- to illustrate how collaborations among academic institutions, fundamentals, and industry partners have evolved to address the therapeutic challenges of these conditions.
CYSTIC FIBROSIS
Within 1989, the discovery of the gene that leads to cystic fibrosis and the cystic fibrosis transmembrane conductance regulator (CFTR) protein10, 10 greatly increased interest within the scientific community in this life-shortening genetic disease, which influences approximately 70, 000 patients worldwide. Along with support from the Cystic Fibrosis Foundation (CFF) and the National Institutes of Health (NIH), researchers swiftly expanded knowledge about the biogenesis, maturation, and function of CFTR, a controlled epithelial anion channel12; such knowledge provided the necessary scientific framework for the development of therapeutic targets. In addition, an international consortium13 determined more than 1700 mutations and defined genotype-phenotype correlations with standard case definitions, 14 which enabled a precision-medicine method to therapeutic development. In the 1990s, attempts were created to treat cystic fibrosis by gene-replacement remedy delivered to airway epithelia. Even though early in vitro15 and in vivo studies16 provided proof of concept, many barriers, including a powerful host immune response, were encountered. 17 These limitations ended such initial clinical development programs.
In the decade following the discovery of the cystic fibrosis gene, scientific knowledge expanded but did not lead to a remedy that corrected CFTR function. In 1999, the CFF launched the Healing Development Program (TDP) to draw both academic and industry partners and commence high-throughput screening for CFTR modulators. 18, 19 The CFF embraced the concept of venture philanthropy9, 20 to boost the interest of industry in an orphan disease. However, the success of the TDP was centered on much more than financial support. 21 The program created a cultural move that allowed the CFF, academic clinicians and experts, federal agencies (the NIH and FDA), and industry to create a strong partnership with common goals and timelines.

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