Use of Anti-aging glycopeptides to enhance beta cell health, survival and improve transplant outcome

a glycopeptide and beta cell technology, applied in the field of anti-aging glycopeptides, can solve the problems of limited supply of beta islet cells for transplantation, unsuitable for widespread application, and insufficient means of preventing islet rejection, so as to improve insulin secretory function and reduce inflammation

Inactive Publication Date: 2021-01-28
PROTOKINETIX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The method improves the survival and function of isolated pancreatic cells, reduces toxicity from immunosuppressants, and enhances engraftment, potentially increasing the success rate of beta islet cell transplantation.

Problems solved by technology

While significant progress has been made in the islet transplantation field, many obstacles remain that currently preclude its widespread application.
Two of the most important limitations are the currently inadequate means for preventing islet rejection, and the limited supply of beta islet cells for transplantation.
Current immunosuppressive regimens are capable of preventing beta islet cells failure for months to years, but the agents used in these treatments are expensive and may increase the risk for specific malignancies and opportunistic infections.
Numerous factors account for substantial graft loss especially in the early phase post intraportal infusion, and insufficient islet mass may limit durable glycemic control in patients.
One factor leading to acute graft loss is hypoxia, as many islets die immediately after transplant before adequate vascularization is re-established.
These factors account for immediate and early islet loss of approximately 60%, resulting in an insufficient islet mass to maintain a functional transplant.
However, there is a paucity of data reflecting potential impact in islet transplantation, where major initial graft lost seems to be unavoidable.

Method used

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  • Use of Anti-aging glycopeptides to enhance beta cell health, survival and improve transplant outcome
  • Use of Anti-aging glycopeptides to enhance beta cell health, survival and improve transplant outcome
  • Use of Anti-aging glycopeptides to enhance beta cell health, survival and improve transplant outcome

Examples

Experimental program
Comparison scheme
Effect test

example 1

Utilizing AAGP™ to Enhance Human Beta Cell Health Initial Characterization

Experiment Methodology

[0321]Research-grade human islet preparations are cultured for 24 hours in the following groups:

[0322]1) AAGP™ supplemented islets cells; and

[0323]2) Controls (non-supplemented islets cells).

[0324]Islets are cultured in humidified atmosphere of 95% air and 5% CO2 at 37° C., at a density of 200 IE / mL using standard tissue culture flask. The AAGP™ concentration is 3 mg / mL. Several tests are conducted on day 1 post-islet isolation, including: Islet recovery, membrane integrity viability stain (Syto® EB) as well as Glucose-Stimulated Insulin Release. The results are shown in FIGS. 1A-D.

example 2

Utilizing AAGP™ to Protect Human Beta Cells from Tacrolimus Toxicity

Experiment Methodology

[0325]Research-grade human islet preparations are cultured for 48 hours in the following groups:

[0326]1) No tacrolimus (Tac−) treated beta islet cells;

[0327]2) Tracrolimus (Tac+) treated beta islet cells; and

[0328]3) Tacrolimus (Tac+) treated+AAGP™ supplementation beta islet cells.

[0329]After 48 h, tacrolimus (10 ng / L) was added to group 2 and 3.

[0330]Islets are cultured in humidified atmosphere of 95% air and 5% CO2 at 37° C., at a density of 200 IE / mL using standard tissue culture flask. AAGP™ concentration is 3 mg / mL. Several tests are conducted on D1 post-islet isolation, including: Islet recovery, membrane integrity viability stain (Syto EB) as well as Glucose-stimulated Insulin Release. The results are shown in FIGS. 2A-F.

example 3

Utilizing Anti-Aging Glyco-Peptides to Improve Transplant Outcome

Experiment Methodology

[0331]Two research-grade human islet preparations are cultured for 24 hours in the following groups:

[0332]1) AAGP™+supplemented islets cells; and

[0333]2) Control (non-supplemented islets)

[0334]Islets are cultured in humidified atmosphere of 95% air and 5% CO2 at 37° C., at a density of 200 IE / mL using standard tissue culture flask. AAGP™ concentration is 3 mg / mL. After 24 h, kidney subcapsular islet transplant is performed on immunodeficient mice (Rag1) with minimal islet mass (1000 IEQ) to assess transplant efficacy (n=4 & 5, control and AAGP™ respectively). The results are shown in FIGS. 3A-G.

Conclusion

[0335]The AAGP™ formulation shows no toxicity on human islet cells.

[0336]AAGP™ seems to enhance islet survival in culture.

[0337]AAGP™ protects islet exposed to tacrolimus in vitro.

[0338]Transplant studies with minimal islet mass were inconclusive, although AAGP™ seems to provide an advantage to tr...

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Abstract

The present disclosure relates to an in vitro method for enhancing engraftment of isolated pancreatic cells comprising the step of contacting an isolated pancreatic cell prior to a transplantation in a subject in need thereof, with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate of the compound of general formula I:

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is filed under 37 CFR 1.53(b) as a continuation application. This application claims priority under § 120 of U.S. patent application Ser. No. 15 / 631,260 filed on Jun. 23, 2017, which claims priority of U.S. patent application Ser. No. 14 / 728,535 filed on Jun. 2, 2015, which claims priority of U.S. provisional patent application 62 / 007,626, filed Jun. 4, 2014, the specifications of which are hereby incorporated by reference in their entireties.BACKGROUND(a) Field[0002]The subject matter disclosed generally relates to the use of anti-aging glycopeptides. More particularly, the subject matter relates to the use of anti-aging glycopeptides to enhance human pancreatic cells engraftment.(b) Related Prior Art[0003]Antifreeze biological compounds, and particularly glycoproteins, exist in the natural environment. These compounds are present for example in some fishes, enabling them to survive in a low temperature environment (i.e....

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): A61K35/39C12N5/071
CPCA61K35/39C12N5/0676C12N2501/90C12N2501/999C12N2501/998A61P1/18A61P3/10
InventorYOUNG, LACHLAN GRANTSHAPIRO, A.M. JAMES
OwnerPROTOKINETIX