Isthmin 1 for treatment of lung inflammation
AssigneeNational University of Singapore
InventorsRuowen Ge, Yin Weng Terence Lam, Wai-Shiu Fred Wong
Life of this patent
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Abstract
Provided herein are polypeptides including an amino acid sequence having at least 70% sequence identity with an Isthmin 1 (ISM1) protein or a GRP78-activating fragment thereof, as well as expressible nucleic acids encoding said polypeptides. Uses of such agents, as well as methods for inducing apoptosis in alveolar macrophages and/or for treating, ameliorating, or preventing inflammation or lung disease such as chronic obstructive pulmonary disease (COPD), emphysema, asthma, acute lung injury (ALI), lung fibrosis, and/or acute respiratory distress syndrome.
Claims5
A method for increasing apoptosis of proinflammatory alveolar macrophages (AM) exhibiting cell surface GRP78 in a subject, said method comprising:
- administering an Isthmin 1 (ISM1) protein GRP78-activating fragment to the subject, wherein the ISM1 protein GRP78-activating fragment consists of:
- (SEQ ID NO:
- 24)
- FEVDMDSCERWMSCKSEFLKKYMHKVINDLPSCPCSYPTEVAYSTADIF
- DRIKRKDFRWKDASGPKEKLEIYKPTARYCIRSMLSLESTTLAAQHCCY
- GDNMQLITRGKGAGTPNLISTEFSAELHYKVDVLPWIICKGDWSRYNEA
- RPPNNGQKCTESPSDEDYIKQFQEAREY;
- or
- (SEQ ID NO:
- 25)
- FEVDTDSCERWMSCKSEFLKKYMHKVMNDLPSCPCSYPTEVAYSTADIF
- DRIKRKDFRWKDASGPKEKLEIYKPTARYCIRSMLSLESTTLAAQHCCY
- GDNMQLITRGKGAGTPNLISTEFSAELHYKVDVLPWIICKGDWSRYNEA
- RPPNNGQKCTESPSDEDYIKQFQEAREY;
- and
- wherein the ISM1 protein GRP78-activating fragment is administered to the lung of the subject via a nebulizer, a metered dose inhaler, or dry powder inhaler.
A method for increasing apoptosis of proinflammatory alveolar macrophages (AM) exhibiting cell surface GRP78 in a subject suffering lung function decline, said method comprising:
- administering an Isthmin 1 (ISM1) protein er-a GRP78-activating fragment to the subject, wherein the ISM1 protein GRP78-activating fragment consists of the following amino acid sequence:
- (SEQ ID NO:
- 24)
- FEVDMDSCERWMSCKSEFLKKYMHKVINDLPSCPCSYPTEVAYSTADIF
- DRIKRKDFRWKDASGPKEKLEIYKPTARYCIRSMLSLESTTLAAQHCCY
- GDNMQLITRGKGAGTPNLISTEFSAELHYKVDVLPWIICKGDWSRYNEA
- RPPNNGQKCTESPSDEDYIKQFQEAREY;
- or
- (SEQ ID NO:
- 25)
- FEVDTDSCERWMSCKSEFLKKYMHKVMNDLPSCPCSYPTEVAYSTADIF
- DRIKRKDFRWKDASGPKEKLEIYKPTARYCIRSMLSLESTTLAAQHCCY
- GDNMQLITRGKGAGTPNLISTEFSAELHYKVDVLPWIICKGDWSRYNEA
- RPPNNGQKCTESPSDEDYIKQFQEAREY;
- wherein the subject suffering lung function decline is confirmed by spirometry or hypoxemia testing;
- and
- wherein the ISM1 protein GRP78-activating fragment is administered to the lung of the subject via a nebulizer, a metered dose inhaler, or dry powder inhaler.
A method for increasing apoptosis of proinflammatory alveolar macrophages (AM) exhibiting cell surface GRP78 in a subject suffering lung function decline, said method comprising:
- determining the alveolar macrophage levels in bronchioalveolar lavage fluid (BALF) of the subject;
- wherein the subject suffering lung function decline is confirmed by spirometry or hypoxemia testing, and higher levels of alveolar macrophages compared to a healthy control subject;
- administering an Isthmin 1 (ISM1) protein GRP78-activating fragment to the subject suffering lung function decline, wherein the ISM1 protein GRP78-activating fragment consists of the following amino acid sequence:
- (SEQ ID NO:
- 24)
- FEVDMDSCERWMSCKSEFLKKYMHKVINDLPSCPCSYPTEVAYSTADIF
- DRIKRKDFRWKDASGPKEKLEIYKPTARYCIRSMLSLESTTLAAQHCCY
- GDNMQLITRGKGAGTPNLISTEFSAELHYKVDVLPWIICKGDWSRYNEA
- RPPNNGQKCTESPSDEDYIKQFQEAREY;
- or
- (SEQ ID NO:
- 25)
- FEVDTDSCERWMSCKSEFLKKYMHKVMNDLPSCPCSYPTEVAYSTADIF
- DRIKRKDFRWKDASGPKEKLEIYKPTARYCIRSMLSLESTTLAAQHCCY
- GDNMQLITRGKGAGTPNLISTEFSAELHYKVDVLPWIICKGDWSRYNEA
- RPPNNGQKCTESPSDEDYIKQFQEAREY;
- and
- wherein the ISM1 protein GRP78-activating fragment is administered to the lung of the subject via a nebulizer, a metered dose inhaler, or dry powder inhaler.
Dependencies are inferred from the claim text.