Preclinical Efficacy of Pyridorin™
The therapeutic potential of Pyridorin™ has now been demonstrated in vivo by extensive preclinical studies that have been carried out in a number of independent laboratories by prominent investigators. These studies have encompassed animal models for the major microvascular diabetic complications of both type 1 (STZ rat) and type 2 diabetes (db/db and KK-Ay/Ta mice models), and have included both preventative and intervention modalities. The latter was established by biopsy prior to treatment in the db/db model.
Pyridorin™ was also shown to significantly prolong survival in diabetic db/db mice. Pyridorin™ has shown efficacy in models of nephropathy, diabetic retinopathy and neuropathy, as well as in atherosclerotic and lipemic (nondiabetic obese) disease.
Preclinical studies of Pyridorin™ include:
- Proof-of-concept AGE albumin-induced nephropathy
- Type 1 diabetes (STZ) rat models of diabetic nephropathy (prevention model), retinopathy (prevention), and neuropathy (intervention)
- Type 2 diabetes mouse models, such as the db/db (intervention after biopsy) and KK-Ay/Ta (prevention)
- Obese Zucker fa/fa rat nephropathy model
- ApoE knock-out STZ diabetic mice model of atherosclerosis (prevention)
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In addition to inhibiting the progression of kidney disease arising from diabetes and diabetes-related pathologies, additional changes were studied and noted during these preclinical studies. These changes included:
- Inhibition of cross-linking of AGE-proteins to the glomeruli of the kidney
- Inhibition of the formation of the prominent AGE carboxymethyllysine (CML) in collagen of kidney and in other tissue (staining)
- Decreased glomerular expression of TGFß1 and decreased deposition of extracellular matrix proteins (collagen, laminin)
- Prevention of loss of heparan sulfate in glomerulus
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