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Breakthroughs in the ability to probe more enhanced understand biologic systems during the past 30 years1-3 have enabled the medical community to build up new healing agents and alter the course of many life-shortening diseases. 4, 5 Despite 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 successfully attaining Food and Drug Administration (FDA) acceptance, 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 a few conditions will have a limited eventual market value, the pharmaceutical industry has been not wanting to initiate early-stage programs to deal with so-called orphan diseases. In recognition of a critical need, federal agencies have developed programs to catalyze innovation and reduce limitations to early advancement new therapies. 8 During the past two decades, disease-focused foundations also have developed a new method to bridging this preclinical gap. Within a process known as venture philanthropy, such foundations have formed partnerships with industry and government agencies to talk about the financial risk of therapeutic development, shorten the early translational pipeline, and advance research with "a concentrate on 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 aide among academic institutions, foundations, and industry partners have evolved to address the therapeutic challenges of these conditions.
CYSTIC FIBROSIS
Inside 1989, the discovery of the gene that causes cystic fibrosis and the cystic fibrosis transmembrane conductance regulator (CFTR) protein10, 11 greatly increased interest within the scientific community in this life-shortening genetic disease, which influences approximately 70, 000 patients worldwide. Together 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 regulated 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 strategy to therapeutic development. Inside the 1990s, attempts were made to treat cystic fibrosis by gene-replacement remedy provided to airway epithelia. Although early in vitro15 and in vivo studies16 provided proof of concept, many barriers, including a powerful host immune response, were encountered. 17 These barriers ended such initial clinical development programs.
In the decade following your 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 Therapeutic Development Program (TDP) to draw both academic and industry partners and start high-throughput screening for CFTR modulators. 18, 19 The CFF embraced the concept of venture philanthropy9, 20 to raise the interest of industry in an orphan disease. However, the success of the TDP was centered on a lot more than financial support. 21 The program created a cultural change 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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