Disease treatment drug based on mesenchymal-stem-cell mobilization

Inventors

Tamai, Katsuto • SHIMBO, Takashi • Yamazaki, Takehiko

Assignees

StemRIM Inc • The University of Osaka

Abstract

The present inventors identified many nuclear proteins contained in the extract of skin tissue by mass spectrometry, randomly selected multiple partial amino acid sequences of the nuclear proteins, chemically synthesized peptides consisting of the partial amino acid sequences, and examined their activity of mobilizing mesenchymal stem cells. As a result, it was found that these multiple peptides show the activity of mobilizing mesenchymal stem cells into peripheral blood, even though their amino acid sequences are completely different from each other. The inventors also found that fragment peptides of the nuclear proteins have therapeutic effects on diseases characterized by inflammation and abnormalities of the immune system (e.g., inflammatory bowel disease and psoriasis). Based on these findings, a new regenerative medicine technology that can overcome the problems of cell transplantation therapy is provided.

Core Innovation

The invention relates to a regenerative-medicine approach using nuclear-protein-derived fragment peptides to mobilize mesenchymal stem cells (MSCs) to peripheral blood. Many chemically synthesized peptides with largely different amino-acid sequences show MSC-mobilizing activity when they are derived from nuclear proteins as fragment peptides, and the peptides are defined by amino-acid sequence identity criteria relative to SEQ ID NOs: 35 to 56.

The disclosed methods administer an effective amount of the specified nuclear-protein fragment peptides to a subject to achieve MSC mobilization to peripheral blood. The problem addressed is mobilizing mesenchymal stem cells to peripheral blood to provide therapeutic effects, in an immune/inflammation-driven disease context.

The described fragment peptides are associated with therapeutic effects in inflammatory bowel disease and psoriasis, as described using a DSS mouse model and an imiquimod ear model, respectively. The document also identifies nuclear proteins whose fragments are used to define the peptide sequences, including basic transcription factor 3 (BTF3), suppressor of Ty 16 Homolog (SUPT16H), Y-box binding protein 1 (YBX1), nucleophosmin 1 (NPM1), proliferation-associated protein 2G4 (PA2G4), prefoldin subunit 5 (PFDN5), proteasome 26S subunit, ATPase 3 (PSMC3), and heterogeneous nuclear ribonucleoprotein K (HNRNPK).

Claims Coverage

The independent claim coverage includes two independent methods that share the central inventive concept of mobilizing mesenchymal stem cells to peripheral blood by administering an effective amount of nuclear-protein fragment peptides with at least 95% sequence identity to sequences in the SEQ ID NOs: 35 to 56 range. Across the independent claims, there are three main inventive elements: sequence identity relative to SEQ ID NOs 35 to 56, the peptide being a fragment of a nuclear protein with MSC-mobilizing activity, and narrowing the nuclear-protein source to specific named nuclear proteins in one independent claim.

The claims cover administration-based methods to mobilize mesenchymal stem cells to peripheral blood using nuclear-protein fragment peptides. The peptide must meet an amino-acid sequence identity criterion relative to SEQ ID NOs: 35 to 56 and must be a nuclear-protein fragment with MSC-mobilizing activity; one independent method further restricts the nuclear protein source to the specifically named eight nuclear proteins.

Stated Advantages

Documented Applications