The first-ever clinical trial of an adeno-associated virus (AAV) gene therapy for type 1 diabetes (T1D) will begin this year, aiming to promote insulin production in muscles – an approach experts hope might offer a durable treatment option without chronic immunosuppression, reports Medscape.
The PROGRESS study will enrol adults with T1D to receive a one-time intramuscular injection of KRIYA-839, and will follow them for one year for both safety and efficacy endpoints.
The product is designed to promote endogenous expression of glucokinase (GCK) and insulin in the quadriceps muscles, said Jeremy Pettus, MD, an endocrinologist and associate Professor of Medicine at the University of California-San Diego, at the 19th International Conference on Advanced Technologies and Treatments for Diabetes (ATTD) 2026, held in Barcelona last week.
“In the type 1 community, we’re used to hearing this will happen in 10 to 15 years’ time, and maybe will come one day. So it’s very exciting to stand here and say that this is actually something that’s in the works and happening now,” he said.
Proven technology
The therapy involves using the non-pathologic AAV vector to deliver two genes, for GCK and insulin, into muscle. These genes then remain in the nuclei of the cells to produce genetic material for the life of the patient.
“It doesn’t integrate with the host genome. It’s not changing the chromosomes,” said Pettus. “This isn’t gene editing or changing genetic make-up.”
Currently approved gene therapy products are mostly for rarer, monogenic diseases. “This is a proven technology,” said Pettus. “And now the manufacturing has improved such that we can move away from the (rare) cases to more common diseases like diabetes.”
Pre-clinical data demonstrated efficacy and safety of both gene products in normalising blood glucose levels in mouse and dog models of T1D without immune suppression for up to four years, he reported.
Advantages of AAV gene therapy include durable clinical benefit, single administration, no need for chronic immunosuppression, and broad patient eligibility.
Unlike current transplants of either cadaver or stem-cell derived islets that require immune suppression and are therefore limited to those with severe hypoglycaemia or recurrent diabetic ketoacidosis, this therapy “could potentially be for the masses” with T1D, the researcher said.
In Kriya’s approach, the two genes within the AAV are delivered into the thigh muscle, where the cells aren’t actively dividing. The muscle then secretes insulin, which activates glucose transporter type 4 to bring glucose into the cells, its normal action.
For its part, GCK is activated at higher glucose levels to move glucose out of the bloodstream, while remaining inactive when blood glucose levels are low. “So it has a glucose sensing kind of quality to it,” Pettus noted.
Treatment administration would require just a short course of “immune modulation” around the response to the virus capsid.
“We’re very careful to use the word ‘modulation,’ not suppression… the idea is to dampen the immune system slightly around the time of injection to help facilitate the uptake of genetic material into the cell,” he said.
Delivery would probably require several intramuscular injections, likely in both legs, over about 30-60 minutes during one outpatient clinic visit. After that, “it takes two to three months to get to a kind of steady state, and then, if all goes well, this could last for the entire life of the patient,” Pettus said.
Kriya’s planned 52-week phase 1 dose escalation study, to begin this year, will enrol patients with T1D who have A1c levels above 7% while using automated insulin delivery systems.
That requirement is for safety, to ensure that insulin dosing can be precisely quantified and de-escalated as needed. But if successful, people who use multiple daily injections would also be eligible, Pettus said.
Potential for a functional cure?
ATTD meeting co-chair Tadej Battelino, MD, Head of the Department of Endocrinology at UCH-UMC Ljubljana, Ljubljana, Slovenia, told Medscape that he wouldn’t use the word “cure” just yet. “I tend to be cautious, so I really can’t give promises….Does this have a potential? Very much so.”
Battelino, who is also Chair and Professor of Paediatrics at the University of Ljubljana, added that even if it’s not a complete “cure”, if it were able to achieve more than 70% of “time in tight range”, i.e, 70-140 mg/dL, possibly in combination with technology, then “I’m not saying it’s a cure, but a functional cure, for sure”.
Medscape article – Gene Therapy to Be Studied for Treating Type 1 Diabetes (Open access)
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