#43 - 🧬 Gene-edited islets, no immuno?

Hey readers! 👋

Welcome back to another week in the T1D world. This one's packed: a major teplizumab trial just dropped results in the NEJM, gene-edited islet cells survived transplantation without immunosuppression (yes, really), and the twiist pump is now fully available across the US. Meanwhile, Roche asked over 4,000 people with diabetes what they actually want, and the answer was loud and clear: tools that predict what's coming next. Let's dig in.

Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes - A phase 3 trial of 328 newly diagnosed children and adolescents found that two 12-day courses of teplizumab preserved beta-cell function, with a 59% higher C-peptide level at 78 weeks compared to placebo. – New England Journal of Medicine

Here's where it gets nuanced, though. Despite that meaningful preservation of beta-cell function, the trial didn't show significant improvements in the clinical outcomes most of us care about day-to-day: insulin dose, A1C, time in range, or hypoglycemia rates. The safety profile was reassuring, with mostly mild side effects. This is an important step in understanding how to protect remaining beta cells early after diagnosis, but it also reminds us that preserving C-peptide doesn't automatically translate to easier daily management. Worth watching as longer-term data emerges.

Gene-modified pancreas cells offer hope for people with type 1 diabetes - A single-patient trial at Uppsala University Hospital showed that gene-edited islet cells, engineered to evade immune rejection, survived transplantation without lifelong immunosuppression. – C&EN

The approach involved knocking out HLA molecules and overexpressing a "don't-eat-me" signal called CD47. It's a proof-of-concept in one patient using cadaveric islets, so we're still early. Scaling this to stem-cell-derived islets, ensuring genomic stability, and figuring out reimbursement are all significant hurdles ahead.

Honest and fair. But the fact that it worked in a human is meaningful.

Modulating immune response for the prevention and treatment of type 1 diabetes - A comprehensive review of immunomodulatory strategies across all four stages of T1D, from antigen-specific tolerogenic therapies in early stages to biomaterial-encapsulated islet transplants for established disease. – PubMed

Researchers embed electronics into stem-cell-derived islet organoids - Scientists created "cyborg" islets by embedding flexible electronics into pancreatic organoids, enabling months-long monitoring of individual beta and alpha cell activity and even electrical stimulation to accelerate maturation. – IEEE Spectrum

This is fascinating from a manufacturing perspective. If you can monitor and tune cell therapies before and after implantation, quality control improves dramatically.

Sequel fully launches twiist automated insulin pump in the US - The twiist AID system is now available nationwide, featuring sound-wave-based insulin measurement, compatibility with multiple CGMs including FreeStyle Libre 3 Plus and Eversense 365, and pricing starting at $0 for the first month with a $50/month cap. – Drug Delivery Business

What stands out here is the flexibility. Multiple sensor options, multiple algorithm choices (including Tidepool Loop and upcoming Diabeloop integration), and a pricing model designed to lower barriers. Sequel reports a 90% reduction in severe hypoglycemia, which is a number worth paying attention to.

AI-driven system aims to eliminate manual meal announcements - Dr. Anas El Fathi received nearly $1M from Breakthrough T1D to develop ABX, an AI system that automates mealtime bolusing without requiring users to announce meals, with a 20-week trial planned for 48 adolescents and young adults. – Center for Diabetes Technology

If ABX works, it could be delivered as a software update to existing pumps. No new hardware needed. That's the kind of practical innovation that actually reaches people.

UVA receives $3.1M NIH grant for ketone-aware insulin delivery - Dr. William Horton's team will develop an AID system that integrates continuous glucose and ketone monitoring, potentially enabling safe use of SGLT inhibitors in T1D. – UVA Center for Diabetes Technology

SGLT inhibitors have shown real kidney and heart benefits but carry ketoacidosis risk in T1D. A dual-sensor approach that watches both glucose and ketones could finally unlock these drugs for our community.

Roche survey reveals demand for predictive diabetes tools - A survey of 4,326 adults with diabetes found that 80% want tools that can predict glucose changes before they happen, while 70% report anxiety about the future and 71% experience frequent fatigue. – Drug Delivery Business

These numbers validate what many of us feel daily. The mental load is real, and the desire for smarter, anticipatory tools isn't a luxury, it's a need.

Juicebox Podcast #1790: Gold Coast - Agatha, an Australian mom, shares how she caught her daughter Ava's T1D early, navigates school management challenges, and uses real-time texting as a tool for proactive insulin adjustments. – Juicebox Podcast

Simple wisdom, powerfully stated.

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