Method for treating cardiac infarction using HMGB1 fragment
Inventors
Tamai, Katsuto • Kamata, Sokichi • Kaneda, Yasufumi • Miyagawa, Shigeru • Sawa, Yoshiki • Yamazaki, Takehiko
Assignees
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Publication Number
US-9623078-B2
Publication Date
2017-04-18
Expiration Date
Abstract
A fragment peptide having a proper length composed of a part of an HMGB1 protein was synthesized and the peptide was confirmed to exhibit therapeutic effects on myocardial infarction.
Core Innovation
The invention relates to pharmaceutical compositions and treatment methods for acute myocardial infarction using HMGB1-derived fragment peptides. In particular, a peptide consisting of amino acids 1–44 (SEQ ID NO: 3) is described as an HMGB1 fragment peptide for administering to a subject in need of myocardial infarction treatment.
The HMGB1 fragment peptide is reported to recruit PDGFRα-positive bone marrow-derived mesenchymal/stem cells to infarct, border, and non-infarction sites after systemic administration. The recruited cell populations are defined in the document, including PDGFRα-positive mesenchymal cells and bone marrow-derived mesenchymal stem cells or related bone marrow-derived cells at the infarct, border, and remote sites.
The document further reports that administration of the HMGB1 fragment peptide suppresses inflammatory cytokine expression, including TNFα and IL-1β, and suppresses long-term left ventricular dysfunction and remodeling. These effects are described in a mouse LAD occlusion model of acute stage infarction.
Claims Coverage
The provided independent claim contains 1 inventive feature centered on administering a specific HMGB1 fragment peptide sequence for myocardial infarction treatment.
Administering an HMGB1 fragment peptide consisting of SEQ ID NO: 3
Administering to a subject in need of treatment an HMGB1 fragment peptide consisting of the amino acid sequence of SEQ ID NO: 3 as a method for treating myocardial infarction.
Overall, the claim coverage in the provided material is directed to treating myocardial infarction by administering the HMGB1 fragment peptide having the amino acid sequence of SEQ ID NO: 3.
Stated Advantages
Recruitment of PDGFRα-positive bone marrow-derived mesenchymal/stem cells to infarct, border, and non-infarction sites.
Suppression of inflammatory cytokine expression, including TNFα and IL-1β.
Suppression of long-term left ventricular dysfunction and remodeling in the described mouse LAD occlusion model.
Improved safety/production rationale via reduced LPS affinity compared with full-length HMGB1.
Improved safety/production rationale via stable chemical synthesis.
Documented Applications
Treatment of acute myocardial infarction using an HMGB1 fragment peptide (SEQ ID NO: 3) in a mouse LAD occlusion model of acute stage infarction.
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