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Abstract: TH-PO224

Allogeneic Neo-Islet (NI) Therapy of Spontaneously Type 1 Diabetic Dogs Durably Reduces Insulin Need and Hyperglycemia and Protects Renal Function: 3 Year Follow-Up From the INAD Study

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Gooch, Anna, SymbioCellTech, Salt Lake City, Utah, United States
  • Chowdhury, Sabiha Sultana, SymbioCellTech, Salt Lake City, Utah, United States
  • Westenfelder, Christof, SymbioCellTech, Salt Lake City, Utah, United States
Background

We published that treatment with allogeneic NIs, organoids of Mesenchymal Stromal Cells and culture expanded islet cells functionally cured the diabetic state in NOD mice without requiring antirejection drugs or encapsulation. Dog and human NIs produced eugylycemia in streptozotocin-diabetic NOD/SCID mice. We tested NI therapy under an FDA guided pilot study (INAD 012-776) in spontaneously diabetic, insulin dependent pet dogs. 6 dogs have been treated and followed for 3 years. We report here the progress of those 6.

Methods

Insulin dependent, diabetic pet dogs were studied: 10 enrolled; 8 treated; 6 followed ≥3 yrs. Pre- and post-treatment sera were tested for islet autoantibodies. Comorbidities and BG were treated. Allogeneic NIs were given once i.p. (2.5x10e5/kg bw) without encapsulation or antirejection agents. Vital signs, BG, insulin need, antibody responses, SCr, BUN, urine protein, lipid profiles, adverse events (AEs) were monitored multiple times for 3 years post-therapy.

Results

3 dogs had pre-treatment islet autoantibodies indicating autoimmunity. 50% of NI treated dogs showed a significant and durable reduction in BG, Fructosamine and HbA1C (12 to 6.8) levels, and 75% showed a significant, durable reduction in daily Insulin requirements (up to 50%). Body weights remained stable; blood pressures were normal. There was no deterioration in renal function, as assessed by SCr and BUN, and no microalbuminuria or proteinuria developed. Hb levels remained normal. Other preexisting comorbidities did not progress.

Conclusion

NIs engraft in the omentum, re-differentiate and physiologically produce and deliver insulin and other islet hormones, and are neither rejected by auto- or allo-immune attacks, as evidenced by (i) absent IgG responses to the administered NIs, and (ii) durably (≥ 3 yrs) improved BG and lowered insulin need. While no dog has achieved insulin independence, preclinical results with human NIs indicate that redosing could accomplish this. NI therapy is feasible, durably effective, and safe as no AEs or SAEs related to therapy have been observed to date. This therapy has significant translational relevance for both dog and human T1DM. A successful Pre-IND meeting has been held, and a human clinical trial is under preparation.

Funding

  • Commercial Support