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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 healing 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, 500 early translational programs successfully attaining Food and Drug Administration (FDA) authorization, at an expense of almost $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 a lot of conditions will have a small eventual market value, the pharmaceutical industry has been not wanting 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 minimize barriers to early development of new therapies. 8 In the past two decades, disease-focused foundations also provide developed a new method to bridging this preclinical gap. Inside 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 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 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 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
In 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 influences approximately seventy, 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 perform of CFTR, a governed epithelial anion channel12; such knowledge provided the necessary scientific framework for the development of therapeutic goals. 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 method to therapeutic development. In the 1990s, attempts were created to treat cystic fibrosis by gene-replacement remedy delivered to airway epithelia. Despite the fact that early in vitro15 and in vivo studies16 provided proof of concept, many barriers, including a powerful 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 Healing Development Program (TDP) to attract both academic and industry partners and also to get started high-throughput screening for CFTR modulators. 18, 19 The CFF embraced the concept of venture philanthropy9, 20 to improve the interest of industry in an orphan disease. However, the success of the TDP was dependent on far more than financial support. 21 The program created a cultural shift 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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