In this week’s issue of The Savvy Diabetic: 

• A Cure for T1D by Disguising Stem Cells?

• Stem Cell-Derived Islets Restore Insulin Production in T1D

• GLP1-RAs and T1D with Open Source AIDs

• FDA Removes Zepbound & Mounjaro from Shortage List

• Teen Receives Teplizumab (Tzield) to Delay Onset of T1D

Scientist hopes to cure Type 1 diabetes by disguising stem cells by Brian Brennan for HealthSciences.arizona.edu, 9 October 2024.

“My whole life I was told a cure is coming and that I won’t have to deal with this very long, but then a cure never came,” said Hannah Pizzato, a principal scientist at the University of Arizona Health Sciences Center for Advanced Molecular and Immunological Therapies. Pizzato was diagnosed with Type 1 diabetes when she was 4 years old.  “We are researching pluripotent stem cells because they can be differentiated into other kinds of cells that perform specialized functions,” Pizzato said. “In theory, these stem cells could be transformed into anything a patient might need. 

Deepta Bhattacharya, PhD and his mentee, Pizzato have spent years trying to find a solution to this problem. Now, “We think modifying stem cells in a way that hides them from the immune system can avoid the need for immunosuppression and potentially make for a effective therapy,” Pizzato said.  Pizzato was the first author on a paper published in Stem Cell Reports earlier this year, in which they genetically engineered stem cells to evade detection by various parts of the immune system, including T cells.

T cells, a type of white blood cell, are key drivers of immune rejection. They are constantly scanning for anything that doesn’t belong in the body, such as viruses and bacteria. T cells even perform security checks on other cells by checking for human leukocyte antigen, a protein found on the surface of most cells. If that protein isn’t a match to the body’s specific human leukocyte antigen, the T cell is triggered to kill that cell. 

“The human leukocyte antigen on transplanted cells is a dead giveaway to T cells that they are not part of the body,” she said. “To get around this problem, we used a genetic engineering tool to cut out the gene that encodes for that protein. This acts as a camouflage to get our modified stem cells around any investigating T cells.”

Read more: Scientist hopes to cure Type 1 diabetes by disguising stem cells

Stem Cell-Derived Islets Show Promise In Another Study from BreakthroughT1D.org, 9 October 2024.

A new study published in Cell and summarized in Nature has shown positive results using stem cell-derived islets to restore insulin production in a patient with type 1 diabetes (T1D). These results add to the mounting evidence that stem cell-derived islets can provide benefits to people with T1D.  The study, conducted by investigators in Beijing, China, involved creating insulin-producing islets from the patient’s own cells. These islets were then implanted behind the abdominal muscles of the patient. This individual was already on immunosuppressive therapy from a liver transplant. They also were experiencing severe hypoglycemic events and hypoglycemia unawareness.

Before the islet transplant, the patient’s time-in-range (TIR), i.e. the percentage of time a person’s blood glucose levels are in the target range, was only 43.81%. Following the transplant, the patient’s TIR soared to over 98% at the one-year mark.  In addition to the substantial increase in TIR, the treatment also eliminated the patient’s severe hypoglycemic events. After just two and a half months, the cells were working as intended, and the recipient no longer needed to administer insulin.

The study in China used autologous cells—derived from the patient’s own body. The key upside to this approach is that, in theory, the recipient would not need immunosuppression because the transplanted cells would not be recognized as foreign and destroyed by the immune system. Potential downsides to autologous cells are they are individualized and cannot be done at scale.

Read more: Stem Cell-Derived Islets Show Promise In Another Study

GLP1-RAs and Type 1 Diabetes: A retrospective study of incretin-based therapy use with Open Source AID by Tim Street for Diabettech.com, 17 October 2024. 

Following a brief review of available research on incretin-based therapies, (a meta-analysis from 2019 and a small study of 10 T1D patients), this appears to be the first investigation into use alongside Automated Insulin Delivery systems and currently the largest associated with current incretin-based treatments. While this is a relatively small sample (n=17) we hope it will provide some indications of the effects people see in use with Automated Insulin Delivery systems. This is a retrospective study of the use of incretin-based therapies with open-source automated delivery systems in the real world.

Amongst those who responded, the biggest impact was a reduction in total daily insulin dose, with 91% of those reporting TDD data seeing a mean reduction of 45%. 59% of respondents reported a reduction in carb announcing/bolusing around mealtimes. Additional benefits included an increase in both TIR and TITR and reduction in hunger.  Adverse side effects included elevated ketone levels, gastrointestinal issues, mental health problems and difficulty in recovering from hypoglycemia.

The messages that come out of this small study are:

• • • • Incretin-based therapies work well alongside AID systems
      • Initial feedback suggests that people do see significant benefits
      • AID systems with some form of meal detection allow users to take a step back from self-management
      • There is a lot we don’t know, and a lot that needs further investigation
      • There are potential issues hiding in plain site that need to be further investigated

Read more: A retrospective study of incretin-based therapy use with Open Source AID

FDA, facing pressure, to review position on Zepbound, Mounjaro shortage by Jonathan Gardner for BioPharmaDive.com, 14 October 2024.

The Food and Drug Administration has temporarily deflected a lawsuit alleging it violated federal law by removing Eli Lilly’s obesity and diabetes drugs Zepbound and Mounjaro from an agency shortage list. In the process, the regulator agreed to evaluate objections from the companies selling compounded copycats of Lilly’s fast-selling medicines.

A ruling issued in the U.S. District Court for the Northern District of Texas permits the makers of compounded versions of tirzepatide, the active ingredient in Zepbound and Mounjaro, to temporarily keep selling their medicines. In the meantime, the FDA and a group of compounders, led by a trade group called the Outsourcing Facilities Association, will continue negotiations. They will file a status report on 21 November 2024.

Read more: FDA, facing pressure, to review position on Zepbound, Mounjaro shortage

12-year-old is first kid in SD to delay Type 1 diabetes with new drug by Paul Sisson for SanDiegoUnionTribune.com, 14 October 2024.

Seventh-grader Mason Webb is the first young person in San Diego, CA to experience what’s possible. The 12-year-old found himself at Rady Children’s Hospital recently, receiving daily infusions for two weeks of Teplizumab, a new drug that the U.S. Food and Drug Administration approved in 2022 to delay the onset of Type 1 diabetes in children and adults.

But there is a catch. In its early stages, diabetes causes no symptoms, but the drug, marketed as Tzield, is only effective during this quiet phase. This is the window when the drug can block the ongoing action of mistargeted white blood cells that, unchecked, cause the immune system to kill insulin-producing beta cells in the pancreas.

Mason is an example of what can happen when developing diabetes is detected early, in what experts call “stage 2.” In his case, a blood test ordered as part of a routine physical detected that his A1C blood sugar score was higher than would be expected for a boy of his age. Had that test instead been ordered to diagnose the cause of symptoms such as extreme thirst and hunger, weight loss and fatigue, it would have been too late. He would have already progressed to stage 3, where beta cells are already damaged, destroying or severely reducing insulin production.

“What’s so exciting is this is the first FDA-approved drug we’ve ever had that can delay onset,” said Dr. Carla Demeterco-Berggren, the pediatric endocrinologist heading up Rady’s Tzield effort. “It’s a big, big deal.”

Read more: 12-year-old is first kid in SD to delay Type 1 diabetes with new drug

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