RFA-DK-13-007 – Cystic Fibrosis Research and Translation Core Center (P30)
Nomination per School: One
Proposals may not be submitted directly by the PI; nominations are submitted by the School’s Research Dean’s Office.
LOI: May 18, 2014
Internal Deadline: April 14, 2014
External Deadline: June 18, 2014
Award Information: Type: Grant
Estimated Number of Awards: 5
Anticipated Amount: Application budgets are limited to $750,000 direct costs per year. Equipment costs and indirect costs on subcontracts are not included in the $750,000 direct cost cap. It is anticipated that the award budget will be directly correlated to the breadth and quality of the research base being served by the Center. The maximum project period may not exceed 5 years.
Materials to Office of Research: Single Page Proposal Summary (0.5” margins; single-spaced; font type: Arial, Helvetica, or Georgia typeface; font size: 11 pt.). CV – (4 pages maximum)
Purpose: This Funding Opportunity Announcement (FOA) invites applications for Cystic Fibrosis (CF) Research and Translation Core Centers. CF Research and Translation Core Centers are designed to support both basic and clinical research on Cystic Fibrosis. CF Research and Translation Core Centers support three primary research-related activities: Research Core services; a Pilot and Feasibility program; and an Administrative Core with an enrichment program. Core Centers provide shared resources to support research to develop and test new therapies for CF and to foster collaborations among institutions with a strong existing research base in CF. The NIDDK currently supports five CF Research and Translation Centers located at institutions with documented programs of research excellence in basic and clinical CF Research. Information about the currently funded CF Research and Translation Centers may be found at http://www3.niddk.nih.gov/centers/all.shtml
Cystic Fibrosis is one of the most common, life-limiting genetic diseases, and is estimated to affect 30,000 Americans. Individuals with CF have inherited two mutated copies of the gene, cystic fibrosis transmembrane conductance regulator (CFTR), in every tissue of the body. Although lung disease is the primary cause of death in CF, multiple organ systems have altered functions including the lung, liver, pancreas, bone, sweat glands, and gastrointestinal and reproductive systems.
Treatment of the pancreatic symptoms and the lung infections has extended median survival in the United States to the mid-thirties. All states in the US now screen for CF at birth to enable presymptomatic support for nutrition and preventing infections that may further improve the quality of life for these patients. Children identified at birth avoid the malnutrition that was the common presenting symptom for CF. In addition, these patients benefit from many new forms of therapy that are being developed to aggressively eradicate bacterial colonization of the lung, control inflammation and lung damage, treat diabetes and liver disease and provide nutritional support.
In addition to treating the symptoms of CF, researchers are investigating molecular and pharmacologic methods to treat the underlying cause of CF. Screening of small molecules has identified lead molecules that increase either expression, processing, trafficking or function of the CFTR protein. This approach has led to the development of the drug, invacaftor (marketed as Kalydeco) which is approved for patients with G551D substitution in CFTR. In addition, other molecules that bind to CFTR are being studied for their ability to correct the most common mutation, deltaF508. Several of these are being tested in clinical trials.
Now that subjects with CF are living longer, there is an increased incidence of CF-related diabetes. In fact, about 40% of patients with CF will develop diabetes by the age of 20. Recent guidelines developed by the Cystic Fibrosis Foundation and the American Diabetes Association suggest that all patients should be screened for the development of diabetes yearly by an oral glucose tolerance test starting at the age of 10. Insulin treatment of CF-related diabetes has been shown to improve survival and lung disease in patients with CF.
Gene therapy approaches to deliver a normal CFTR gene are also being pursued. New vectors with less toxicity have been developed. The availability of improved animal models such as the pig and ferret, which better mimic the human disease, aid in the testing of these new therapies. These encouraging findings suggest that collaborative efforts between basic and clinical researchers could foster the translation of novel basic research findings into preclinical testing in animal models, and potential clinical applications.
CF research often requires the use of specialized technologies and resources to support a cohesive research effort. The goal of the Center is to make state-of-the-art technologies and resources readily accessible to a broad spectrum of investigators working on CF.