US-20260124275-A1 - METHODS OF TREATING DIABETES AND RELATED COMPLICATIONS

US20260124275A1US 20260124275 A1US20260124275 A1US 20260124275A1US-20260124275-A1

Abstract

A method of treating diabetes or a related complication in a subject in need thereof, the method comprising: administering a therapeutically effective amount of epithelial mitogen or a functional fragment thereof to the subject. The method can be used to lower the amount of circulating glucose in the subject by enhancing glucose uptake by hepatocytes and myocytes in an insulin-dependent and independent manner, and pancreatic beta cell regeneration.

Inventors

Chi Ming Wong
Ka Ying CHAN

Assignees

THE HONG KONG POLYTECHNIC UNIVERSITY

Dates

Publication Date: 20260507
Application Date: 20241107

Claims (13)

1 . A method of treating diabetes or a related complication in a subject in need thereof, the method comprising: administering a therapeutically effective amount of epithelial mitogen (Epigen) or a functional fragment thereof to the subject.
2 . The method of claim 1 , wherein the diabetes is type I diabetes, type II diabetes, type I pre-diabetes, or type II pre-diabetes.
3 . The method of claim 1 , wherein the related complication is selected from the group consisting of glucose intolerance, hyperglycemia, insulin resistance, reducing fat mass, pancreatic beta cell dysfunction, hypertension, cardiovascular diseases comprising hypertension, heart attack, and stroke, diabetic nephropathy, diabetic retinopathy, diabetic vasculopathy, diabetic neuropathy, blindness, kidney failure, diabetic foot and lower limb amputation and combinations thereof.
4 . The method of claim 1 , wherein the Epigen comprises a polypeptide having at least 95% sequence homology with SEQ ID NO: 1 or SEQ ID NO: 2.
5 . The method of claim 1 , wherein the Epigen comprises a polypeptide having at least 98% sequence homology with SEQ ID NO: SEQ ID NO: 1 or SEQ ID NO: 2.
6 . The method of claim 1 , wherein the Epigen comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: SEQ ID NO: 1 or SEQ ID NO: 2.
7 . The method of claim 1 , wherein the Epigen comprises a polypeptide having SEQ ID NO: SEQ ID NO: 1 or SEQ ID NO: 2.
8 . The method of claim 1 , wherein the Epigen consists of a polypeptide having SEQ ID NO: SEQ ID NO: 1 or SEQ ID NO: 2.
9 . The method of claim 1 , wherein the Epigen is a recombinant Epigen.
10 . The method of claim 1 , wherein the Epigen is in isolated form.
11 . The method of claim 1 , wherein the diabetes is type I diabetes or type II diabetes and the consists of a polypeptide having SEQ ID NO: 1 or SEQ ID NO: 2.
12 . The method of claim 1 , wherein the Epigen is administered intravenously, intraperitoneally, or intramuscularly, orally, or subcutaneously.
13 . The method of claim 1 , wherein the subject is a human.

Description

REFERENCE TO SEQUENCE DISCLOSURE The sequence listing identified as “Sequence_Listing_P26296US00” in XML file format having a file size of 8.0 KB created on Oct. 16, 2024, filed herewith, is incorporated herein by reference in its entirety. TECHNICAL FIELD The present disclosure relates to methods for treating diabetes and related complications. BACKGROUND Diabetes is a growing global health concern, with increasing prevalence in both wealthy and relatively more developed countries. The primary underlying causes are impaired insulin production and reduced insulin utilization effectiveness. Over time, the elevated glucose levels characteristic of diabetes can lead to a range of serious complications, including heart attack, stroke, blindness, kidney failure, and lower limb amputation. These complications place a significant burden on healthcare systems and society as a whole. Unfortunately, there is currently no complete cure for diabetes. Patients with mild to severe diabetes must typically rely on medications to help maintain their blood glucose levels within a healthy range. Diabetes drugs can be categorized by their mechanisms of action and/or routes of administration. Protein-based therapeutics, such as glucagon-like peptide (GLP-1) agonists, have emerged as a promising class of diabetic treatments. These agents tend to have more targeted therapeutic actions, lower side effect profiles, and are generally better tolerated compared to some traditional small-molecule drug options. Two examples are Liraglutide (marketed as Victoza) and Exenatide (marketed as Byetta), both of which have been used clinically for the management of diabetes. The use of insulin secretion stimulants, while effective for some types of diabetes, still has some concerning associated issues. Studies have suggested that primary insulin hypersecretion can actually lead to beta cell dysfunction, as seen in patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) who have genetic mutations causing excessive insulin release. In fact, a recent study indicated that an autosomal dominant mutation in the sulfonylurea receptor-1 (SUR1) causing congenital hyperinsulinism can subsequently result in insulin-deficient diabetes, representing a new genetic subclass of type 2 diabetes with similar characteristics of glucose intolerance, beta cell dysfunction, and hyperglycemia. In vitro studies have also suggested that chronic treatment of beta cells with insulin secretagogues, such as sulfonylureas, can induce cell death through apoptosis. Conversely, allowing beta cells to “rest” by reducing insulin secretion could be beneficial and protect against glucose toxicity and oxidative stress. This helps explain the high failure rate of current first- and second-line diabetes therapies, where up to 15-34% of patients fail at 5 years. Alternative approaches to treating diabetes that do not solely rely on stimulating insulin secretion are therefore needed. In contrast to type 2 diabetes, type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells, rendering patients unable to naturally regulate their blood sugar. As a result, agents that stimulate insulin secretion cannot be used to treat type 1 diabetes. Management of type 1 diabetes is challenging, requiring constant monitoring of blood sugar and insulin administration via injections or pump. Even with careful management, type 1 diabetes patients remain at significant risk of long-term complications. Finding effective treatments to improve quality of life for these patients is a crucial priority. Therefore, there is an unmet need for an effective drug for both type 1 and type 2 diabetes that eliminates or at least diminishes the disadvantages and problems described above. The epidermal growth factor receptor (EGFR) and its ligands have been implicated in the pathogenesis of diabetes. Studies have shown that EGFR and its ligands, such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), play a role in insulin resistance, pancreatic beta-cell function, and glucose homeostasis. Dysregulation of the EGFR signaling pathway has been associated with the development and progression of both type 1 and type 2 diabetes. Therefore, EGFR ligands have great potential in the development of new therapeutic strategies targeting this pathway. There is thus a need for improved methods for treating diabetes that address or overcome at least some of the disadvantages described above. SUMMARY Accordingly, in a first aspect of the present disclosure provides a method of treating diabetes or a related complication in a subject in need thereof, the method comprising: administering a therapeutically effective amount of epithelial mitogen (Epigen) or a functional fragment thereof to the subject. In certain embodiments, the diabetes is type I diabetes, type II diabetes, type I pre-diabetes, or type II pre-diabetes. In certain embodiments, the related complication is s