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Discoveries 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 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, 000 early translational programs efficiently reaching Fda (FDA) approval, at an expense of almost $1 billion. 6 The majority of therapeutic development fails in the preclinical phase, which is sometimes described as the "valley of dying. "7
For this reason and because therapies for a lot of conditions will have a limited eventual market value, the pharmaceutical industry has recently been not wanting to initiate early-stage programs to treat so-called orphan diseases. In recognition of a critical need, federal agencies have developed programs to catalyze innovation and minimize barriers to early development of new therapies. 8 In the past two decades, disease-focused foundations likewise have developed a new approach 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 give attention to 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 concentrate on 3 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
In 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 75, 000 patients worldwide. Along with support from the Cystic Fibrosis Foundation (CFF) and the National Institutes of Health (NIH), researchers rapidly 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 targets. In addition, an international consortium13 recognized 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. 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 clinical development programs.
In the decade after 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 draw both academic and industry partners and also to start 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 far more than financial support. 21 The program created a cultural change 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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