The projects detailed elsewhere in this application address important steps in the development of effective new therapies for CF, and five or more of them require a dependable source of freshly isolated and cultured respiratory epithelium from humans affected with CF and from controls. Some projects also require ready access to a standardized measurement of nasal potential difference (NPD) in these same two groups of subjects. Therefore, CORE B-Clinical Resources has as its first aim to recruit and coordinate CF patients and controls for clinical studies.
The second aim i s to provide normal and cystic fibrosis (CF) human cells to investigators in a timely manner and sufficient quantity to meet their needs.
The third aim i s to provide to investigators participating in this project measurements of CF gene product (CFTR) function, such as NPD, and of clinical status in CF and non-CF subjects. The Core also continually reviews and improves specimen collection and NPD techniques, and adds new related capabilities as needed for affiliated projects. Because these cells originate in the respiratory tract they are especially relevant to CF lung disease. The freshly isolated and cultured respiratory epithelial cells serve in model systems for testing candidate correctors and potentiators of mutant CF genes and CFTR, and for studies of non-viral gene delivery. The NPD results from unidirectional transport of ions across the respiratory epithelium by ion-selective channels, including CFTR. Thus, measuring the response of NPD to selected agonists and antagonists of ion transport reflects the function of CFTR in vivo. In the short term, NPD provides a baseline measure of CFTR function in CF subjects and controls. In the long term, NPD provides an in vivo measure of the impact of CFTR activators and potentiators in future human trials. The primary sources of human tissue specimens and the NPD measurements are the UCSF Cystic Fibrosis Center and other clinics at UCSF. Subjects, CF and normal, are recruited from these clinical programs after referral to this Core by care providers.
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