Kidney Week

Abstract: TH-PO191

A Second Dose of Allogeneic Neo-Islets (NIs) Further Reduces Insulin Need and HbA1c and Preserves Renal Function Long Term in Autoimmune T1DM Pet Dogs (INAD 012-776)

Session Information

• Diabetic Kidney Disease: Clinical - I
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Gooch, Anna, SymbioCellTech, Salt Lake City, Utah, United States

Anna Gooch,

• Westenfelder, Christof, SymbioCellTech, Salt Lake City, Utah, United States

Christof Westenfelder,

Background

Spontaneously T1D dogs, like T1D humans, never spontaneously revert to a non-diabetic state. Their insulin needs remain stable or increase. They experience progressive CKD, hyperlipidemia, hepatic steatosis, diabetic neuropathy and retinopathy, malignancies, hypoglycemic events, and other complications, making them an ideal translational model for T1DM.
We reported (n=8 dogs) that one dose of Neo-Islets (NIs), organoids of Mesenchymal Stromal Cells (MSCs) and culture expanded Islet Cells, when administered i.p. engraft in the omentum where they physiologically secrete insulin and other islet hormones, thereby reducing the need for insulin in autoimmune, spontaneously T1DM pet dogs by up to 50% for up to 3 years. As the MSC component is immune-modulatory, NIs require no antirejection drugs. Here we demonstrate that NIs’ beneficial effects are enhanced through administration of a 2^nd dose.

Methods

4 of the original 8 NI-treated, autoimmune diabetic dogs were administered a second dose of 2x10e5 NIs/kg bw i.p. at various times post the first dose. Dogs were assessed for antibodies to NIs, changes in serum glucose, HbA1c, insulin need, liver and renal function, blood counts, adverse and serious adverse events and their relation to administration of the study drug.

Results

A dog who had been unresponsive to the first dose of NIs received a 2^nd dose 4 years post the 1^st dose. 1 year later, she has a 25% reduced need for insulin, and a 17% reduction in serum glucose. Of the 3 dogs re-dosed within a year of the first administration, insulin need has decreased 25- 50%, and serum glucose levels decreased 40-59%. HbA1c levels are ~4 percentage points reduced, and within normal range. No significant changes in renal function, serum chemistries or blood counts have been observed in the 2-12 months since redose. No dog has developed antibodies to NIs subsequent to either dose. No AEs or SAEs have been attributed to NI therapy.

Conclusion

Allogeneic-NI therapy, which delivers insulin physiologically, is safe durably effective, requires no anti-rejection drugs, can be safely re-administered, and preserves renal function long term. As with human islet transplants, redosing potentiates therapeutic efficacy, and several doses may be required to achieve insulin independence.

Funding

• Commercial Support – SymbioCellTech