Screening

Screening for T1D is one pathway to prevention, but has many factors that need to be considered. JDRF recognizes the importance of universal screening for T1D since approximately 90% of people diagnosed with T1D have no family history. Now that the first disease-modifying therapy has been approved in the USA (Teplizumab, brand name: Tzield), screening may provide an opoprtunity to delay diagnosis. Furthermore, with early identification and close monitoring of individuals with early-stage, pre-symptomatic T1D, DKA rates at the time of T1D diagnosis are reduced from 25-62% to just 4-6%1.

Globally, JDRF-I is funding nearly 20 studies on T1D genetic risk scores and autoantibody screening.  In Canada, Dr. Despoina Manousaki holds a JDRF-I grant to update the existing T1D genetic risk score algorithm to better reflect Canada’s diverse population. In this portfolio, JDRF-C also supports general population autoantibody screening as part of the Israel Screening Project. These grants will compliment and inform the new Canada-wide Screening Research Consortium funded in collaboration with CIHR.

1Alonso GT, Coakley A, Pyle L, Manseau K, Thomas S, Rewers A. Diabetic ketoacidosis at diagnosis of type 1 diabetes in Colorado children, 2010-2017. Diabetes Care 2020;43:117–121
Duca LM, Wang B, Rewers M, Rewers A. Diabetic ketoacidosis at diagnosis of type 1 diabetes predicts poor long-term glycemic control. Diabetes Care 2017;40:1249–1255
Winkler C, Schober E, Ziegler AG, Holl RW. Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies. Pediatr Diabetes 2012;13:308–313

Disease-Modifying Therapies

Disease-modifying therapies for type 1 diabetes aim to halt or slow the progression of the disease, rather than just manage symptoms. These treatments focus on preserving beta cells in the pancreas and/or suppressing the immune response against beta cells, thereby promoting their survival. Tzield (Teplizumab) is the first approved disease-modifying therapy for T1D, approved by the FDA in November 2022.

In our global portfolio, we support multiple Canadian researchers that are examining beta cell regeneration and immunotherapies for T1D. Dr. Jan Dutz, with the JDRF Centre of Excellence at UBC is conducting clinical trials of Ustekinumab, a therapy that is already approved for psoriasis and Crohn’s disease under the brand name Stelara. This study will determine if Ustekinumab can protect remaining beta cells at the time of T1D diagnosis to prevent or minimize the need for insulin supplementation. In collaboration, Dr. Megan Levings holds a JDRF-I grant to harmonize the biomarkers in the Canadian Ustekinumab trials (in adults) with a similar study being completed in the UK (in youth). Other projects include:

Dr. Robert Screaton is examining beta cell regeneration (regrowing functioning beta cells in a T1D pancreas).

Dr. Shirley Wu is developing a nanoparticle delivery product to deliver therapeutic agents directly to the pancreatic islets for the purpose of restoring beta cell function.

Cell Therapy

Canada boasts one of the foremost scientific programs for islet donor transplantation and stem cell therapy for T1D. In 1999 the Edmonton Protocol was developed at the University of Alberta to implant donor islet cells via the portal vein (liver) into patients with severe T1D. Dr. James Shapiro led the team that developed the Edmonton protocol, and by 2000 the first results were published on the first 7 patients, who were insulin-independent after an average of 12 months. As of 2022, over 250 patients have been treated using the Edmonton Protocol with 79% reaching insulin-independence for some duration following transplantation.

 

In 1961, stem cell transplantation was discovered by Canadians James Till and Ernest McCulloch, and since then we have been leading the charge on stem cell-derived islet therapy.  Dr. Doug Melton (Harvard, JDRF-funded) and Dr. Tim Kieffer (UBC, JDRF-funded) simultaneously and separately developed protocols to derive beta cells from stem cells in 2014.  Since then, Canada has been at the forefront of developing optimized stem cell-derived islet-like cells for transplantation.  The following are some grants in our global portfolio that are supporting cell therapy:

Dr. James Shapiro (lead of the Edmonton Protocol team at the University of Alberta), has two grants in our global portfolio to continue improving islet transplantation by reducing or removing the requirement for immunosuppression.

Dr. Gregory Korbutt (member of the Edmonton Protocol team at the University of Alberta) is working on a drug delivery system that will help enhance the success of islet transplantation, as well as examining the use of porcine (pig) stem cells for islet transplantation.

Dr. Andras Nagy and Dr. Tim Kieffer are working to integrate Dr. Nagy’s two patented technologies – FailSafe™ and “immunocloaking” – to develop functional and safe insulin-producing islet cell transplants from human stem cells.

Dr. Michael Sefton is examining the skin as a site for islet cell transplantation by developing regenerative biomaterial for immune protection and vascularization to promote cell growth.

Dr. Robert Screaton is examining a class of genes that contribute to beta cell survival or death. By pinpointing which genes have an impact, cells can be gene-edited to improve the likelihood of survival.

Improving Lives

JDRF’s global research strategy has four components in the improving lives portfolio: drugs (insulins and adjunctive therapies), devices (artificial pancreas systems and components), complications (including kidney, eye disease, and heart), and mental health (including therapies for the psychosocial burden of T1D).

Canadian researchers conducting improving lives research in the global portfolio include:

Dr. Ahmad Haidar is conducting clinical trials to test whether a novel dual-hormone (insulin and pramlintide) artificial pancreas can eliminate carb counting and lead to easier management of T1D.

Dr. Mahla Poudineh is developing a new biosensor that will be capable of continuously measuring blood ketones and glucose simultaneously.

Dr. Tricia Tang has Canadian and Global grants contributing to her work on REACHOUT, a virtual, peer-support intervention to improve the mental health of people with T1D in remote and rural areas of British Columbia.