Purpose

Praetego is committed to offering clinically meaningful drug candidates to patients at risk for developing significant neurodegenerative diseases, starting with Alzheimer’s Disease. Praetego’s Amadorins are proprietary and highly potent small molecules affecting multiple targets:

1. The Amadorins arrest the Advanced Glycation End-product (AGE) pathway at a critical initial stage thus minimizing downstream damage.

2. They inhibit oxidative damage of redox metal ions that leads to toxicity.

3. They minimize damage and thus boost the body’s protection mechanisms.

The Amadorins offer systemic protection because they inhibit some of the earliest drivers of pathology throughout the body. Praetego’s Amadorins are designed to preserve function. This approach could transform the experience of Alzheimer’s Disease.

 


 

AGE Pathway

Glucose (sugar) is the universe fuel for metabolism, but unfortunately it also binds with proteins and lipids. The resulting unstable products of this binding are susceptible for oxidative breakdown (glycoxidation). The body uses redox metal ions (iron, copper) to catalyze this chemical breakdown process. AGEs are the toxic result of the breakdown.

We all generate AGEs as a normal side-product of metabolism. When we are healthy, the body counters AGE damage and suppresses the deleterious effects of AGE accumulation. As we age, become ill, or experience trauma, the body’s ability to manage AGEs is diminished. We simply cannot keep up with the overproduction of AGEs.

Once formed, AGEs are irreversible. They pile up throughout the body; in small blood vessels, the brain, eyes, and even the kidneys. AGEs are instigators of pathology. As AGEs accumulate, they eventually signal an inflammatory response and impact tissue integrity. AGE accumulation promotes Oxidative Stress and Oxidative Stress promotes more AGE formation. This cycle is a powerful instigator of damage to the nervous system, the vascular system, and many other organs in the body.

 

Amadorins Inhibit the AGE Pathway

Praetego’s technology inhibits AGE formation at the initial step.  The Amadorins are upstream inhibitors of the oxidative breakdown of glycated proteins (glycoxidation). They bind to the redox metal ions driving the oxidation and render them unable to catalyze oxidation. The key is not removing them completely (chelation), as redox metal ions are necessary for normal biochemical activity. They are not bad actors on their own when bound inside proteins and enzymes as essential cofactors. The Amadorins circulate in plasma addressing AGE-mediated pathology from released metal ions.

The Amadorins are unique from traditional pharmacotherapy since they do not bind to specific protein receptors. By addressing the triggering pathology via chemical intervention, they provide systemic biological protection.

 

Neurodegeneration and the Link to Serious Diabetic Complications

The role of AGEs in neurodegenerative diseases has been well characterized. The risk of dementia and the most common form, Alzheimer’s Disease, increases as we age. Even in the absence of disease, AGEs are accumulating in tissue throughout the body over time.  

Serious Diabetic Complications are exacerbated by chronic insults to the vascular system from high blood glucose feeding the AGE pathway.  However, there is a growing body of evidence indicating that neurodegeneration occurs before microvascular changes in serious diabetic complications. This is apparent in research conducted on Diabetic Peripheral Neuropathy and Retinopathy. The connection to and contribution of the AGE pathway is most evident when considering that Diabetics are far more likely to develop AD.