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Innovations 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 change 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 successfully reaching Fda (FDA) approval, at a cost of practically $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 few conditions will have a limited eventual market value, the pharmaceutical industry has already been hesitant to initiate early-stage programs to deal with so-called orphan diseases. In recognition of a critical need, federal firms have developed programs to catalyze innovation and minimize barriers 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 relationships with industry and federal agencies to share the financial risk of therapeutic development, shorten the early translational pipeline, and advance research with "a concentrate on individual, 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.
Within this review, we will give attention to about 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
Within 1989, the discovery of the gene that leads to 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 impacts approximately seventy, 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 functionality 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 recognized 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. Even though early in vitro15 and in vivo studies16 provided proof of concept, many barriers, including a strong 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 bring about a remedy that corrected CFTR function. In 1999, the CFF launched the Restorative Development Program (TDP) to draw both academic and industry partners and get started 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 based on far more than financial support. 21 The program created a cultural move that allowed the CFF, academic clinicians and researchers, federal agencies (the NIH and FDA), and industry to create a strong partnership with common goals and timelines.

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