Request for Information (RFI): Human Cellular Models as Experimental Tools to Predict Individual Responses to CFTR-directed Therapeutics for Cystic Fibrosis Lung Disease

Notice Number: NOT-HL-14-221

Key Dates
Release Date: April 4, 2014
Response Date: May 7, 2014

Related Announcements
None

Issued by
National Heart, Lung, and Blood Institute (NHLBI)

Purpose

The National Heart, Lung, and Blood Institute (NHLBI) seeks feedback from the small business community regarding the current state of the science and commercial feasibility of using in vitro human cellular models as an experimental tool for predicting in vivo drug responses to cystic fibrosis transmembrane conductance regulator (CFTR)-directed therapeutics for Cystic Fibrosis (CF) lung disease at the individual level.  Responses to this Request for Information (RFI) will assist NHLBI staff in assessing the value of the research in areas related to advancing precision medicine approaches to treatment.

Background

A variety of corrector and potentiator drugs are being developed for treatment of ion transport defects in epithelial cells of patients with CF.  Because the reversal of ion transport defects will probably be incomplete with any particular drug and because of substantial clinical and genetic variation among patients with CF (even those with the same CFTR mutation), it is likely that multiple drugs will ultimately be required for each patient and that the optimal choice of drugs will be highly individualized.  Hence, patients with CF may benefit significantly from a precision medicine approach to their treatment.

In vitro cellular systems that reproduce ion transport defects due to mutations in CFTR have proven very useful for high throughput screening of drugs for the treatment of CF.  Such in vitro cellular assays may also be useful for predicting the therapeutic responsiveness of particular individuals to a given drug, but this possibility has not yet been tested.  That latter application would require development of cellular assay systems that can be produced efficiently with cells obtained from each patient, that predict the clinical benefit of CFTR-targeted drugs, and that retain phenotypic characteristics of the donor subjects which reflect their individual responsiveness to the drug(s). Research is needed to develop and validate these in vitro cellular systems and associated diagnostic assays, especially as applied to early disease in infants and young children with CFTR mutations, since that population may benefit most from the use of in vitro assays to select therapies.
Recent improvements in methods for epithelial cell culture may now allow rapid, large-scale expansion of human epithelial cells from a small biopsy/tissue brushings and maintenance in culture of airway phenotypes from the native epithelium (e.g., cell polarity, ion transport, formation of ciliated cells, and mucus secretion).  Technical specifics (e.g., source of epithelial cells, air-liquid interface versus organotypic 3-D cultures as bronchospheres, readouts for ion transport properties, etc.) have not yet been optimized for this type of application.  Hence, research is needed for both development and validation of in vitro human cellular systems as predictive biomarkers of in vivo drug response in the context of CF.  This research may represent a timely opportunity for small businesses, given the well-defined need for clinical application in CF and the potential for this disease to serve as a model for precision medicine with implications for other conditions. 

Information Requested

This RFI seeks feedback from the small business community regarding the current state of the science and the commercial feasibility of this approach to use human cellular systems to test individual responsiveness to CFTR-directed therapeutics for CF lung disease, especially in airway cells derived from tissue samples obtained from young children. Comments can include but are not limited to the following areas:

1.  The current state of the science in this area, identifying what additional research, if any, is needed for translation and commercialization, and indicating whether the small business community (as opposed to academic research centers) is able to and interested in conducting this research.

2.  Readiness of the small business community to translate and commercialize technologies related to use of in vitro human cellular models as experimental tools to predict responses to CFTR-directed therapeutics for CF lung disease on an individual patient level.

3.  Identification of challenges/barriers to commercialization, if any. 

Confidentiality

Response to this RFI is voluntary.  All interested parties are invited to respond, especially small businesses engaged in biotechnology research.  Any personal identifiers (e.g., names, addresses, e-mail addresses, etc.) will be removed when responses are compiled.  Only the de-identified comments will be used.  Proprietary, classified, confidential, or sensitive information should not be included in your response.  The United States government reserves the right to use any non-proprietary technical information in any resultant funding opportunity announcement(s).

This RFI is for information and planning purposes only and should not be construed as a funding opportunity announcement or as an obligation on the part of the United States government to provide support for any ideas identified in response to it.  Please note that the United States government will not pay for the preparation of any information submitted or for its use of that information.  Responses will be compiled and shared internally with staff from the NHLBI, and with the National Heart, Lung, and Blood Advisory Council, with one or more subcommittees of the Council, and with scientific working groups convened by the NHLBI, as appropriate.  In all cases where responses are shared, the names of the respondents will be withheld.

How to Submit a Response

Responses to the RFI will be accepted until May 7, 2014.  You will not receive individualized feedback on any suggestions.  No basis for claims against the United States government shall arise as a result of a response to this request for information or from the Unites States government’s use of such information.

All comments must be submitted via email as text or as an attached electronic document.  Microsoft Word documents are preferred.  Please submit your response to: schleges@nih.gov.

Inquiries

Please direct all inquiries to:

Susan Banks-Schlegel, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0202
Email: schleges@nih.gov

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