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Discoveries in the ability to probe more enhanced understand biologic systems in the past 30 years1-3 have enabled the medical community to develop 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, 1000 early translational programs efficiently obtaining Food and Drug Administration (FDA) authorization, at a cost of almost $1 billion. 6 Many 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 lot of conditions will have a small eventual market value, the pharmaceutical industry has been hesitant to initiate early-stage programs to deal with so-called orphan diseases. In recognition of a critical need, federal companies have developed programs to catalyze innovation and minimize barriers to early progress new therapies. 8 During the past two decades, disease-focused foundations also provide developed a new strategy to bridging this preclinical gap. Within a process known as venture philanthropy, such foundations have formed relationships with industry and federal government agencies to share 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 trials and assistance from disease-specific experts in study design, which has helped in bridging the gap in therapeutic development.
With this review, we will give attention to three 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
In 1989, the discovery of the gene that causes cystic fibrosis and the cystic fibrosis transmembrane conductance regulator (CFTR) protein10, eleven greatly increased interest within the scientific community in this life-shortening genetic disease, which influences approximately seventy, 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 perform 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 described genotype-phenotype correlations with standard case definitions, 14 which enabled a precision-medicine method to therapeutic development. Within the 1990s, attempts were made to treat cystic fibrosis by gene-replacement remedy shipped to airway epithelia. Although 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 medical development programs.
In the decade after 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 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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