LOOP PEPTIDE AND TGF alpha FOR STIMULATING STEM CELL PROLIFERATION AND MIGRATION

Abstract

There is disclosed a novel genus of small peptides, smaller than human TGFα, identified as having TGFα biological activity and therefore being useful as pharmacologic agents. It is further disclosed that both TGFα and the genus of small peptides disclosed herein have therapeutic activity to stimulate hematopoiesis, e.g., in patients undergoing cytotoxic cancer chemotherapy, and also act as cytoprotective agents to protect patients undergoing cancer cytotoxic therapy from gastrointestinal (GI) side effects, such as mucositis, and otherwise to support the barrier function of the GI tract, such as when it is harmed by cytotoxic therapy.

Description

TECHNICAL FIELD OF THE INVENTION[0001]The present invention provides a novel peptide that is derived from a loop or “lollipop” region of transforming growth factor alpha (TGF-α) and is biologically active for causing stem cells to proliferate and migrate. The present invention further provides a method for augmenting hematopoiesis, particularly trilineage hematopoiesis, and a method for suppressing immune functioning associated with autoimmune diseases, and a method for suppressing inflammatory responses mediated (in part) by excessive histamine release, comprising administering an effective amount of a TGF-α a polypeptide or a fragment thereof, such as the lollipop region. The present invention further provides a method for treating or preventing mucositis and gastrointestinal side effects in patients undergoing cancer treatment, comprising administering an effective amount of a TGF-α polypeptide or a fragment thereof, such as the lollipop region.BACKGROUND OF THE INVENTION[0002]Th...

AI Technical Summary

Benefits of technology

[0011]The present invention is based upon two basic discoveries that have not been reported before in the literature of TGFα. Firstly, a novel genus of small peptides, much smaller than (50 amino acid human) TGFα, was discovered as having TGFα biological activity and therefore are useful as pharmacologic (therapeutic) agents for the same indications as full-length TGFα polypeptide (50 or 57 amino acids). Secondly, TGFα and the genus of smaller peptide fragments disclosed herein, were found to have therapeutic activity to stimulate hematopoiesis in patients undergoing cytotoxic cancer chemotherapy and to act as a cytoprotective agent to protect a patient undergoing cancer cytotoxic therapy from gastrointestinal (GI) side effects, such as mucositis and otherwise support the barrier function of the GI tract when it is harmed by cytotoxic therapy.

Problems solved by technology

This “side effect” reduces the tolerated dose of such drugs as it can cause a breakdown of the GI barrier function and septic condition in a patient already immuno-compromised.

This can also lead to life-threatening hemorrhage.

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