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Identification of Therapeutic Peptides for Asthma

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43HL093903-01
Agency Tracking Number: HL093903
Amount: $228,220.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: PHS2007-2
Solicitation Year: 2008
Award Year: 2008
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
BOSTON, MA 02118
United States
DUNS: 126775860
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 () -
Business Contact
Phone: (617) 638-4103
Research Institution

DESCRIPTION (provided by applicant): The primary treatment for asthma is inhaled steroids which is not uniformly effective and has the potential for long-term side effects. Based on the activity of IL-16 in asthmatic inflammation, we have identified a nov
el immunotherapeutic approach. Asthmatic inflammation is absolutely dependent on the recruitment and activation of CD4+ T cells into the lung following allergen provocation. IL-16 stimulation of CD4+ T cells, by virtue of its direct interaction with CD4 an
d disruption of CD4 aggregation, results in significant inhibition of CD4+ T cell activation and Th2 cytokine production. Administration of IL-16 in a murine model of allergic asthma is immunomodulatory with a 90-95% decrease in airway hyperreactivity (AHR
) and inflammation. We investigated whether a peptide derived from the bioactive site of IL-16 could mimic the immunomodulatory effect and serve as a new therapeutic modality. Our Preliminary Data show that a 16 residue peptide (ST-P1) disrupts CD4 aggr
egation in vitro. Moreover, aerosolized administration of ST-P1 peptide to mice results in a 75% reduction in AHR and inflammation, which is similar to treatment with IL-16 (whole protein). We hypothesize that additional CD4-binding peptides can be generat
ed that bind to the same IL-16 binding site on CD4, with equal or greater avidity. These peptides will inhibit the asthma model with greater efficacy than the ST-P1 peptide. The goal of this proposal is to identity a peptide that can inhibit asthmatic infl
ammation as well as, or better, than IL-16 protein. The advantage of peptide therapy versus whole IL-16 protein is three fold: 1) a peptide would not have the potential agonistic effect of IL-16 on CD4+T cell recruitment; 2) a peptide would likely have bet
ter airway distribution due to its smaller size; and 3) a peptide would be less expensive to produce than the whole molecule. The aims for this Phase I application are to 1) screen and synthesize peptides derived from a phage displayed combinatorial pep
tide library, as well as logically derived peptides based on the IL-16 sequence; 2) test the peptides for their ability to bind to CD4 and disrupt T cell activation; 3) screen the best peptides from Aim 2 in the murine asthma model to identify maximal inhi
bition and identification of a lead compound. This peptide will then represent a novel, steroid independent, modality for asthma therapy which will be used for further development and GMP production as part of a Phase II application. PUBLIC HEALTH RELEV
ANCE: These studies will identify a new generation of drug candidates for treating asthma. The drug, a peptide, would be inexpensive to produce, easily administered to the lungs and have potentially no side-effects. This immune-based strategy represents a
novel approach to asthma therapy which would potentially replace the use of inhaled steroids.

* Information listed above is at the time of submission. *

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