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Breakthroughs in the ability to probe and better understand biologic systems in the past 30 years1-3 have enabled the medical community to produce new therapeutic agents and alter 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, 500 early translational programs effectively reaching Fda (FDA) authorization, at a cost of almost $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 recently been hesitant to initiate early-stage programs to take care of so-called orphan diseases. In recognition of a critical need, federal firms have developed programs to catalyze innovation and reduce limitations to early development of new therapies. 8 Previously two decades, disease-focused foundations also have developed a new approach to bridging this preclinical gap. Within a process known as venture philanthropy, such foundations have formed relationships with industry and government agencies to talk about the financial risk of therapeutic development, shorten the early translational pipeline, and advance research with "a give attention to human, 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.
In this review, we will concentrate on three diseases -- cystic fibrosis, multiple myeloma, and type 1 diabetes mellitus -- to illustrate how collaborations among academic institutions, foundations, and industry partners have evolved to address the therapeutic challenges of these conditions.
CYSTIC FIBROSIS
Within 1989, the discovery of the gene that causes 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 impacts approximately 70, 000 patients worldwide. Together with support from the Cystic Fibrosis Foundation (CFF) and the National Institutes of Health (NIH), researchers quickly expanded knowledge about the biogenesis, maturation, and functionality of CFTR, a controlled epithelial anion channel12; such knowledge provided the necessary scientific framework for the development of therapeutic focuses on. In addition, an international consortium13 discovered more than 1700 mutations and identified genotype-phenotype correlations with standard case definitions, 14 which enabled a precision-medicine approach to therapeutic development. Within the 1990s, attempts were created to treat cystic fibrosis by gene-replacement remedy provided to airway epithelia. Despite the fact that early in vitro15 and in vivo studies16 provided proof of concept, many barriers, including a robust host immune response, were encountered. 17 These obstacles ended such initial scientific development programs.
In the decade following the discovery of the cystic fibrosis gene, scientific knowledge expanded but did not cause a remedy that corrected CFTR function. In 1999, the CFF launched the Therapeutic Development Program (TDP) to attract both academic and industry partners also to commence high-throughput screening for CFTR modulators. 18, 19 The CFF embraced the concept of venture philanthropy9, 20 to improve the interest of industry in an orphan disease. However, the success of the TDP was centered on far more than financial support. 21 The program created a cultural move that allowed the CFF, academic clinicians and scientists, federal agencies (the NIH and FDA), and industry to create a strong partnership with common goals and timelines.

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