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US-20260124282-A1 - DECORIN FOR ITS USE IN THE TREATMENT OF DIABETES

US20260124282A1US 20260124282 A1US20260124282 A1US 20260124282A1US-20260124282-A1

Abstract

Decorin or a composition containing decorin for use in the treatment of type 1 diabetes, type 2 diabetes or gestational diabetes is described herein. Decorin or a composition containing decorin is also described for use in the context of transplanting pancreatic islet cells.

Inventors

  • Karim BOUZAKRI
  • Michel PINGET

Assignees

  • CENTRE EUROPEEN D'ETUDE DU DIABETE

Dates

Publication Date
20260507
Application Date
20251121
Priority Date
20181219

Claims (16)

  1. 1 . A method for increasing the quality and/or survival duration of pancreatic islet cells of a donor, wherein the method comprises: administering, to the donor, a pharmaceutical composition comprising one or more of decorin, a nucleic acid sequence encoding the decorin, or a vector comprising a nucleic acid sequence encoding the decorin.
  2. 2 . The method according to claim 1 , wherein the donor is not diabetic.
  3. 3 . The method according to claim 1 , wherein the donor is a human.
  4. 4 . The method according to claim 1 , wherein the donor has a weight greater than 10 kg.
  5. 5 . The method according to claim 1 , wherein the donor is an age that is less than 65 years.
  6. 6 . The method according to claim 1 , comprising: removal of pancreatic islet cells from the donor after administration of the pharmaceutical composition.
  7. 7 . The method according to claim 6 , wherein the pancreatic islet cells are cultured in a medium comprising decorin after removal from the donor.
  8. 8 . The method according to claim 6 , wherein the pancreatic islet cells are subjected to a genetic manipulation that transfers either a nucleic acid sequence encoding decorin or a variant thereof, or a vector comprising a nucleic acid sequence encoding decorin or a variant thereof into the pancreatic islet cells.
  9. 9 . A method for preparing pancreatic islet cells for transplantation in a diabetic patient comprising: removing pancreatic islet cells from a donor subject or inducing stem cells into pancreatic islet cells; and purifying the pancreatic islet cells removed from the donor subject or induced from the stem cells, wherein during at least one of the removing, inducing or purifying, the pancreatic islet cells are in ex vivo contact with a medium or a composition comprising decorin, a nucleic acid sequence encoding decorin or a variant thereof, or a vector comprising a nucleic acid sequence encoding decorin or a variant thereof.
  10. 10 . The method of claim 9 , comprising: culturing the purified pancreatic islet cells in a cell culture medium containing decorin.
  11. 11 . The method according to claim 9 , wherein the the removing of the pancreatic islet cells, the inducing of the stem cells into pancreatic islet cells and the purifying of the pancreatic islet cells are conducted in a presence of decorin.
  12. 12 . The method according to claim 9 , wherein the donor subject is pretreated with a pharmaceutical composition comprising one or more of decorin, a nucleic acid sequence encoding the decorin, or a vector comprising a nucleic acid sequence encoding the decorin before removal of the pancreatic islet cells.
  13. 13 . The method according to claim 9 , comprising: forming a graft from the purified pancreatic islet cells in a presence of decorin.
  14. 14 . The method according to claim 9 , wherein the pancreatic islet cells removed from the donor subject or induced from the stem cells are subjected to a genetic manipulation that transfers either a nucleic acid sequence encoding decorin or a variant thereof, or a vector comprising a nucleic acid sequence encoding decorin or a variant thereof into the pancreatic islet cells.
  15. 15 . The method according to claim 10 , wherein the cultured pancreatic islet cells have an apoptosis rate of at most 6% per 1000 cells.
  16. 16 . A method for treating diabetes, wherein the method comprises: administering, to a subject in need thereof, a pharmaceutical composition comprising decorin in combination with an immunosuppressive therapy, an anti-inflammatory treatment or an antidiabetic active ingredient, wherein the immunosuppressive therapy and/or the anti-inflammatory treatment is selected from anti-TNFα, RAPAMUNE™ (sirolimus), calcineurin inhibitors, T cell depleting agents, or combinations thereof, and wherein the antidiabetic active ingredient is selected from metformin, sulfonylureas, tolbutamide, acetohexamide, tolazamide, chlorpropamide, glibenclamide, glimepiride, glipizide, gliclazide, glycopyramide, gliquidone, alpha-glucosidase inhibitors, acarbose, miglitol, voglibose, thiazolidinediones, pioglitazone, rosiglitazone, meglitinides, repaglinide, nateglinide, incretino-mimetic, a glucagon-like peptide analog, exenatide or its derivatives, taspoglutide, liraglutide, semaglutide, a dipeptidyl peptidase-4 inhibitor, vildagliptin, sitagliptin, saxagliptin, linagliptin, allopigezine, dapagliptin, canamycin analog, palmlintide, a sodium glucose transporter inhibitor, emagliflozin, dapagliptin, canamycin, or a combination thereof.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application is a divisional of U.S. patent application Ser. No. 17/416,130 filed on Jun. 18, 2021, which is a U.S. National Stage Application of PCT/FR2019/053186 filed on Dec. 19, 2019, which claims the benefit of priority of French patent application FR1873296 filed on Dec. 19, 2018, the entire contents of all of which are hereby incorporated by reference. SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Nov. 21, 2025, is named 0078223-000026.xml and is 5,625 bytes in size. TECHNICAL FIELD The present disclosure relates to the field of health and more particularly concerns the treatment of diabetes. TECHNOLOGICAL BACKGROUND Currently, a person dies from diabetes every six seconds. In 2017, the estimation of the WHO reports that there are 466 million people with diabetes worldwide and 3.5 million in France (in addition between 500,000 and 800,000 with diabetes do not know). Diabetes is a chronic disease that appears when the pancreas does not produce enough insulin or that the organism does not properly use the insulin it produces. This results in a disorder of the assimilation, the use and the storage of the glucose supplied during the various meals of the day. This results in an increase in the blood glucose level, which is hyperglycemia. According to the World Health Organization (WHO), if the blood glucose level is greater than 1.26 g/L fasting, then the patient is diabetic. There are many forms of diabetes, the main ones being type 1 diabetes, type 2 diabetes and gestational diabetes. Type 1 diabetes, also known as insulin-dependent diabetes, occurs after the destruction of the insulin-producing pancreatic cells by the patient's immune system: beta cells. This results in a significant decrease in the amount of insulin produced by the body, thus causing an increase in the blood glucose level. There are many acute symptoms, in particular a polyuria (excessive excretion of urine), a polydipsia (intense thirst), a constant hunger and a weight loss. To treat diabetic patients, several therapeutic solutions exist. The first option is insulin therapy, based on the multi-daily administration of insulin by injection with an insulin pen or by infusion with insulin pumps. This type of treatment is highly constraining and strongly impacts the quality of life of patients. The second option is pancreatic transplantation. This surgical treatment is reserved for diabetic patients with severe kidney complications and who need to undergo dialyses. In this case, the pancreas graft is generally associated with the grafting of another organ, in general the kidney. The operation has the advantage of completely replacing the insulin injections. It therefore leads to improved quality and life expectancy, as well as a reduction in diabetes-related complications. Unfortunately, this technique has many limitations, such as the rejection of the graft, the need for lifelong immunosuppressant treatment, infections or internal haemorrhages. In addition, there is a very heavy surgical procedure under general anesthesia, presenting a non-negligible risk of morbidity. The third option is the transplantation of pancreatic islets. This approach involves transplanting pancreatic secretory cells into a diabetic recipient. This technique makes it possible to eliminate certain limits of the pancreas graft, by transplanting only the endocrine fraction of the pancreas: the cells of the pancreatic islets. This alternative has the advantage of being minimally invasive, rapid and causes fewer complications related to the surgical procedure. It ensures the stabilization of glucose metabolism, a significant decrease in severe hypoglycemic episodes and the normalization of glycated hemoglobin levels (Shapiro A. M. et al., 2000, The New (Shapiro A. M. et al., 2000, The New England Journal of Medecine, No343, p. 230-238.; Pepper A. R. et al., 2013, World Journal of Transplantation, No3, p. 48-53). England Journal of Medecine, No343, p. 230-238.; Pepper A. R. et al., 2013, World Journal of Transplantation, No3, p. 48-53). This technique is particularly recommended for patients whose diabetes is particularly unstable (severe hypoglycemia, coma episodes) thus bringing into play their vital prognosis, for which the injections of insulin are not a possible therapeutic approach. Pancreatic islet transplantation is carried out in several stages. First, the donor's pancreas is surgically removed and transported to a facility able to perform the isolation of the pancreatic islets. Mechanical and enzymatic digestion is performed to separate the various tissues that compose the pancreas. The islets are purified and separated from the other tissues by a discontinuous gradient of Ficoll. Said isolated islets are cultured for 12 to 48 h before being transplanted