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Alzheimer’s is a Multifactorial Disease—The Risk Increases with Age

Alzheimer’s disease (AD) is a public health crisis growing exponentially as our population ages. In the U.S., AD affects 1 in 9 adults over the age of 65. It affects 1 in 2 over 85 years of age. Research has demonstrated that the disease starts two decades before a formal diagnosis is made. Beyond the hallmark  amyloid ‘plaques’ and tau ‘tangles’, neurodegeneration is a multifactorial process starting long before obvious cognitive decline.

The Problem of Glucotoxicity

Glucose is the universal fuel for metabolism. As a undesirable consequence of metabolism, glucose binds with proteins and lipids. This binding produces unstable byproducts (Amadori Intermediates) that are susceptible to oxidative breakdown (glycoxidation and lipoxidation). The breakdown is non-enzymatically catalyzed by redox metal ions (iron, copper) and produces Advanced Glycation End-products (AGEs).

 

AGEs, often called glycotoxins, cause both acute and chronic harm. The formation of AGEs produces Reactive Oxygen Species (ROS), which promotes oxidative stress. The long-term accumulation of AGEs throughout the body can damage both form and function of tissue. 

 

AGE formation is accelerated by hyperglycemic conditions, namely diabetes and other conditions, which occur with increased frequency in aging, and especially in AD. 

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THE SOLUTION

Amadorins Limit Glucotoxicity

Praetego’s Amadorins are unique upstream inhibitors of the oxidative breakdown of glycated proteins and lipids (glycoxidation and lipoxidation). We call them chemical protectants because they interfere with redox metal ions that catalyze this oxidative reaction. Amadorins circulate in the bloodstream, constantly interrupting the formation of AGEs. Thus, they protect the whole body from glucotoxicity.

 

A feature of PTG-630’s chemical structure allows them to bind and cap the redox metals. Capping, rather than removing, is what differentiates the Amadorins from chelators. It’s also a strong rationale for an ideal safety profile for a chronic use drug

 

Praetego’s Amadorins are designed to work systemically to preserve function. This approach could transform the experience of Alzheimer’s disease and other chronic diseases of aging.

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PTG-630 has demonstrated the ability to:

Increase synaptic density in AD patient derived neuronal cell culture

Reverse cognitive decline in long-term transgenic animal models of AD

Reduce Amyloid levels in animal models of AD

Reduce tau biomarker levels (ptau202) in an animal model of tauopathy

Mechanistic Proof

We know the Amadorins work as chemical protectants because they have worked in humans. The original Amadorin was effective against Diabetic Nephropathy, a disease associated with AGE pathology, as demonstrated in clinical trial data.  

PTG-630 is a First-In-Class small molecule for early intervention against Alzheimer’s disease.
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Novel Small Molecule Therapeutics for Age-Related Dementias

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INTERESTED IN OUR WORK?

Praetego is committed to developing patient-centric drugs to limit neurodegenerative diseases associated with aging.

Praetego is focused on developing novel drugs that are potent, well-tolerated, and cost-effective.
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