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Breakthroughs in the ability to probe more enhanced understand biologic systems in the past 30 years1-3 have enabled the medical community to produce 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, 000 early translational programs successfully reaching Food and Drug Administration (FDA) authorization, at an expense of practically $1 billion. 6 Most therapeutic development fails in the preclinical phase, which is sometimes described as the "valley of dying. "7
For this reason and because therapies for some conditions will have a limited eventual market value, the pharmaceutical industry has 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 progress new therapies. 8 Previously 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 federal government agencies to share the financial risk of therapeutic development, shorten the early translational pipeline, and advance research with "a give attention to individual, 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.
Within this review, we will give attention to 3 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, 10 greatly increased interest within the scientific community in this life-shortening genetic disease, which impacts approximately 75, 000 patients worldwide. With support from the Cystic Fibrosis Foundation (CFF) and the National Institutes of Health (NIH), researchers quickly 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 discovered 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 shipped to airway epithelia. Although early in vitro15 and in vivo studies16 provided proof of concept, many barriers, including a strong host immune response, were encountered. 17 These limitations 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 Restorative Development Program (TDP) to attract 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 a lot more than financial support. 21 The program created a cultural shift 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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