Presenter of 3 Presentations
Levicure Ltd. is a start-up that provides orally administered therapy that facilitates remission of T1DM
T1DM REMISSION AND Β-CELL REGENERATION, INDUCED BY ORAL ADMINISTRATION OF TRIPLE-DRUG COMBINATION OF DPP-4 INHIBITOR, PPI, AND GABA IN NOD MICE. A PROOF-OF-CONCEPT
Abstract
Background and Aims
Our concept views T1DM as an immune-triggered neurodegenerative disorder of the endocrine pancreas. Our previous pilot studies in adults have shown that with triple therapy (TT) insulin demands were reduced by 59%, in parallel with a significant reduction of HBA1C and without weight loss. 31.6% of participants entered a long-term remission and became insulin-free.
Methods
We studied 150 NOD mice for a total of 268 days, including the observation period, two main experiments which lasted 70 days and included the treatment arm, prevention arm and crossover. After 99 days (supervision), 51 animals became diabetic and were randomly assigned to five groups: ABC; AB; AC; BC, and Placebo (A - GABA; B – Sitagliptin; C – Omeprazole).
Results
The ABC group demonstrated the best effect compared to other combinations. On day 71 the ABC vs Placebo groups showed: Blood Glucose (BG) 15.7 ± 7.7 and 27.3 ± 10.2 nmol/l (p=0.036); C-peptide 0.96 ± 0.54 and 0.42 ± 0.77 nmol/l (p= 0.022); insulin 7.09±2.72 and 3.20±3.27 nmol/l (p=0.018); Insulin/Glucagon ratio 0.19 ± 0.07 and 0.09± 0.09 (p=0.021); exogenous insulin demands 0.3 ± 0.9 and 1.8 ± 1.4 units/mice (p=0.009) respectively. Immunohistochemistry analysis demonstrated the elevated number of insulin – producing cells in ABC group when compared to Placebo.
Conclusions
TT has resulted in significant improvement in the clinical, laboratory, and morphological parameters in NOD mice. 55% of animals in the ABC group have entered remission. All-in-all this study is proof of concept and efficacy of the new T1DM treatment approach.
PREVENTION OF T1DM, INDUCED BY ORAL ADMINISTRATION OF TRIPLE-DRUG COMBINATION OF DPP-4 INHIBITOR, PPI, AND GABA IN NOD MICE. A PROOF-OF-CONCEPT
Abstract
Background and Aims
T1DM prevention remains the challenge. Studies dedicated to this issue are almost exclusively aimed at the immune system; the results are mainly disappointing or insufficient to draw definite conclusions. Our concept views T1DM as an immune-triggered neurodegenerative disorder of the endocrine pancreas. Our previous studies in NOD mice and humans have shown the effectiveness of triple therapy (TT) in β-cell preservation and regeneration.
Methods
We studied 150 NOD mice for a total of 268 days. After 99 days of the supervision period, the 94 animals who remained healthy were randomly assigned to five groups: ABC; AB; AC; BC, and Placebo (A - GABA; B – Sitagliptin; C – Omeprazole). The duration of the study was 70 days
Results
The ABC group demonstrated the best effect compared to other combinations. On day 71, the average metrics of ABC vs Placebo groups showed: Number of mice who remained healthy:17 vs. 9 (p=0.004); Blood Glucose (BG) 9.9±6.2 vs. 19.0±7.8 mmol/l (p=0.001); C-peptide 1.8 ± 0.3 vs. 0.8 ± 0.7 nmol/l; Glucose/insulin ratio 1.2 ± 1.6 vs. 5.5 ± 5.5 (p= 0.001); Glucose/C-peptide ratio 6.3 ± 7.7 vs. 112.1 ± 193.3 respectively (p=0.001); The prevention rate of the onset of T1DM was 66% in ABC group compared to placebo (p= 0.0048).
Conclusions
TT can effectively prevent T1DM in NOD mice. All in all, this is a proof-of-concept of our method.
