2020 Year in Review: DRI Progress Report

From unpredictable and unprecedented to challenging and surreal, 2020 was a year like no other. And while it tested our fortitude and transformed the way we work, it never once distracted us from our singular mission. At the Diabetes Research Institute and Foundation, we have one goal – to find a cure for diabetes.

The need for a cure has never been more urgent, as COVID-19 has disproportionately affected the diabetes community, who often suffer more extreme complications from the

virus if infected. As vaccines to combat coronavirus are becoming available, we have seen what can be done with enough public support, need and effort – and it fuels our relentless commitment to get this job done.

Driven by the mantra, Hope Isn’t Quarantined, our scientific faculty and staff, many of whom are personally affected by type 1 diabetes (T1D), continued to make progress, publish research papers in medical journals, and monitor ongoing experiments throughout the year with a strategic focus on curing diabetes.

Below is a synopsis of the year’s progress in both clinical and translational research efforts, as we approach 2021 with a view toward the future.

• We have promising preliminary results demonstrating the safety and efficacy of a novel, clinical grade anti-CD154, which appears extremely promising in preventing the progression of islet transplant rejection. We plan to test the antibody in combination with mesenchymal stem cells (MSCs). The objective is to further prolong islet survival in the absence of traditional immunosuppressive drugs, and we anticipate that a clinical trial will begin in the year ahead.

• Using an islet transplant study model, we recently demonstrated that co-transplantation of insulin-producing islets with MSCs significantly prolonged rejection and overall islet survival. Our observations confirm that the MSCs are potent immunomodulators that can alter the functioning of the immune system and help to restore balance.

• Two breakthrough discoveries made last year provided a window into the pancreas’s ability to regenerate. Using analysis of samples from the tissue network nPOD, DRI scientists confirmed the existence of pancreatic stem cells in patients with diabetes, regardless of the duration of the disease. Additionally, they developed a method allowing the long-term culture of human pancreatic slices, which could lead to a faster and more certain path to clinical trials for T1D and T2D.

• The POSEIDON trial, testing Vitamin D and highly purified Omega-3 fatty acids, continued to show extremely exciting results because of its safety profile, wide availability of the agents, and accessibility for children. We are currently evaluating the data at one-year post-enrollment, and new patients are currently being screened for participation.

• After presenting our 20-year islet transplant patient survival data at the American Diabetes Association’s 2020 Scientific Sessions, a paper was approved for publication in Diabetes Care reporting on survival analysis. Our data indicated a cumulative proportion of islet survival greater than 80% at 20 years post islet cell transplant. This is significantly better than previously reported data from patients of a similar age group who did not receive islet transplants.

• The DRI is studying small molecules called microRNAs as markers to predict the risk of diabetes and the progression of diabetes after diagnosis. The findings will be essential to conduct more efficient clinical trials and test new therapies more rapidly and with fewer participants. At the same time, we are investigating the impact of microRNAs on insulin production by beta cells, which could help lead to therapeutic interventions.

• There has been strong evidence that low doses of IL-2, a molecule produced by the body, can address several autoimmune conditions. DRI researchers are planning to test this in combination with another agent, ATG, to stop the attack on the insulin-producing cells in patients who are still producing some insulin. A full clinical protocol has been developed, in collaboration with six clinical sites and additional research laboratories. A National Institutes of Health (NIH) grant is being prepared for submission, and this trial is expected to start recruiting in 2022.

• DRI scientists have developed a novel encapsulation strategy to improve oxygen supply and reduce inflammation. This innovative method has the potential to align with stem-cell therapies and cell-based treatments that are nearing the clinical stage.

• Another important project aims at identifying small molecules that can modulate protein-protein interactions (PPls) and can become therapeutic alternatives for eliminating immunosuppression. The importance of PPIs, in regard to immune responses, has already been demonstrated in oncology research. We are exploring their ability to dampen the immune response against transplanted islets and native beta cells as a possible treatment for islet transplant recipients and for the prevention/reversal of T1D onset.

• Since anti-rejection drugs can be harsh on the body, localized immunosuppression limited to the site of the islet transplant could be a safer solution for patients. Emerging technologies such as nanomaterials (materials that rely on very small, nano-sized components) have enormous potential to help achieve such targeted, local drug and essential nutrient delivery. Therefore, we are exploring nanomaterial-based delivery systems that are localized to the vicinity of the insulin-producing implants. Additional immunoengineering platforms for beta cell replacement are also being tested, with the goal of reducing or eliminating immunosuppression in patients with T1D.

While this is not an exhaustive list of research projects, it highlights the many avenues we are exploring to find a cure for diabetes now. To keep abreast of our work, please sign up to be a DRI Insider.

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