COMPOSITIONS AND METHODS FOR PROTECTING TYPE 2 ALVEOLAR EPITHELIAL CELLS (AEC2)
Provided herein are compositions comprising caveolin-1 (Cav-1) peptides and methods of using said compositions to protect type 2 alveolar epithelial cells from injury- or disease-induced apoptosis as well as increase the expression of the ABCA3 and SpC proteins.
1 - 2 . (canceled)
3 . A method of increasing the expression level of ATP-binding cassette sub-family A member 3 (ABCA3) protein and/or surfactant protein C (SPC) in the lung epithelium in a patient in need thereof, the method comprising administering to the patient in need thereof an effective amount of a pharmaceutical composition comprising a polypeptide comprising the amino acid sequence of FTTFTVT (SEQ ID NO: 2).
4 . (canceled)
5 . The method of claim 3 , wherein the patient has infant respiratory distress syndrome, pulmonary inflammation, chronic obstructive pulmonary disorder, acute lung injury, a lung infection, chemical-induced lung injury, plastic bronchitis, asthma, acute respiratory distress syndrome, inhalational smoke induced acute lung injury, bronchiolitis, bronchiolitis obliterans, a fibrotic condition of the lungs, or interstitial lung disease, or wherein the patient is undergoing chemotherapy or radiation therapy.
6 - 20 . (canceled)
21 . The method of claim 5 , wherein the interstitial lung disease is idiopathic pulmonary fibrosis.
22 . (canceled)
23 . The method of claim 3 , further comprising administering at least one additional therapeutic to the patient.
24 . The method of claim 23 , wherein the at least one additional therapeutic is an NSAID, steroid, DMARD, immunosuppressive, biologic response modulators, or bronchodilator.
25 . The method of claim 3 , wherein the patient is a human.
26 . The method of claim 3 , wherein the polypeptide consists of the amino acid sequence of FTTFTVT (SEQ ID NO: 2).
27 . The method of claim 3 , wherein the polypeptide has the amino acid sequence of FTTFTVT (SEQ ID NO: 2) and 1-5 additional amino acids at the N-terminus and/or C-terminus.
28 . (canceled)
29 . The method of claim 3 , wherein the polypeptide comprises the amino acid sequence of ASFTTFTVT (SEQ ID NO: 3), wherein the polypeptide comprises at least one N- and/or C-terminal addition lacking identity to SEQ ID NO: 2.
30 . The method of claim 29 , wherein the polypeptide comprises at least one amino acid added to the N-terminus and/or C-terminus.
31 - 32 . (canceled)
33 . The method of claim 3 , wherein the polypeptide comprises at least one non-standard amino acid, and optionally, wherein the non-standard amino acid is ornithine.
34 - 35 . (canceled)
36 . The method of claim 3 , wherein the polypeptide comprises an N-terminal and/or C-terminal modification.
37 - 38 . (canceled)
39 . The method of claim 36 , wherein the N-terminal modification is acylation and/or the C-terminal modification is amidation.
40 . (canceled)
41 . The method of claim 3 , wherein the polypeptide comprises the amino acid sequence of KASFTTFTVTKGS (SEQ ID NO: 4), KASFTTFTVTKGS-NH2 (SEQ ID NO: 5), aaEGKASFTTFTVTKGSaa (SEQ ID NO: 6), aaEGKASFTTFTVTKGSaa-NH2 (SEQ ID NO: 7), OASFTTFTVTOS (SEQ ID NO: 9), or OASFTTFTVTOS-NH2 (SEQ ID NO: 10).
42 - 45 . (canceled)
46 . The method of claim 3 , wherein the polypeptide comprises the amino acid sequence of Ac-aaEGKASFTTFTVTKGSaa-NH2 (SEQ ID NO: 8).
47 . (canceled)
48 . The method of claim 3 , wherein the polypeptide further comprises a cell-penetrating peptide (CPP).
49 . The method of claim 48 , wherein the CPP comprises an amino acid sequence selected from the group consisting of GRKKRRQRRRPPQ (SEQ ID NO: 21), RQIKIWFQNRRMKWKK (SEQ ID NO:22), and GIGAVLKVLTTGLPALISWIKRKRQQ (SEQ ID NO:23).
50 . The method of claim 3 , wherein the polypeptide maintains the biological activity of caveolin-1 (Cav-1).
51 . The method of claim 3 , wherein the polypeptide is a multimer comprising at least two polypeptides according to claim 3 .
52 . The method of claim 51 , wherein a first polypeptide of the at least two polypeptides is essentially identical to a second polypeptide of the at least two polypeptides.
53 . The method of claim 51 , wherein a first polypeptide of the at least two polypeptides is not identical to a second polypeptide of the at least two polypeptides.
54 . The method of claim 3 , wherein the polypeptide comprises L-amino acids.
55 . The method of claim 3 , wherein the polypeptide comprises at least one D-amino acid.
56 . The method of claim 3 , wherein the polypeptide is capped at the N- and/or C-terminus.
57 . (canceled)
58 . The method of claim 3 , wherein the pharmaceutical composition is formulated for lung instillation.
59 . The method of claim 58 , wherein the pharmaceutical composition is micronized using air-jet milling.
60 . The method of claim 58 , wherein the pharmaceutical composition is formulated as a nebulized solution.
61 . The method of claim 3 , wherein the pharmaceutical composition is administered intranasally, intrabronchially, or intrapleurally into the lungs of the patient.
62 . The method of claim 3 , wherein the pharmaceutical composition is formulated for systemic administration.
63 . (canceled)
64 . The method of claim 3 , wherein the pharmaceutical composition is administered by instillation into the lungs of the patient.