Chemo Brain in Breast Cancer
Also known as Cancer-related Cognitive Decline (CRCD) and Chemo-induced Cognitive Impairment (CICI), ‘Chemo brain’ is a common and debilitating side effect of cancer treatment. It can start during treatment and linger long after cancer treatment is complete. In Breast Cancer, the high prevalence of chemo brain impacts every aspect of daily life – parenting, working, and social engagement. There is no FDA approved drug and the need grows as more women survive Breast Cancer treatment only to be left with significant cognitive side effects.
Making matters worse, patients who experience chemo brain may have an increased risk of developing dementia. Chemo brain and dementia share many pathological mechanisms.
Among the routine activities of metabolism to generate energy to fuel cells, oxidation is a constant process. Essential metals such as copper and iron (redox metals) catalyze these reactions. Oxidation produces Reactive Oxygen Species, or ROS. When a significant amount of ROS are produced, it leads to a greater insult called Oxidative Stress.
There are different kinds of oxidative reactions. Glycoxidation uses redox metals to catalyze the oxidation of glycated proteins and lipids. This reaction produces ROS and another problematic product called Advanced Glycation End-products (AGEs).
Oxidative Stress and AGE pathology are particularly harmful in the case of diabetes. With an excess of glucose to generate glycated proteins, AGEs accumulate in vulnerable tissue and contribute to serious diabetic complications such as retinopathy, peripheral neuropathy, and nephropathy. As diabetics age, the cycle of oxidative stress and AGE production serves as a pathological basis for disease progression.
As metabolism is a universal process, all bodies are subjected to oxidative stress and AGEs. Aging and illness make us more vulnerable to this pathology. In addition, some cancer therapies are known to produce oxidative stress as a byproduct of how they work to kill cancer cells. Excessive oxidative stress is harmful, especially to the brain. This side effect of chemotherapy can impact cognitive function and lead to chemo brain.
PTG-630 has demonstrated the ability to:
Increase synaptic density in APOE4 (+) AD patient derived neuronal cell culture
Reverse cognitive decline in long-term transgenic animal models of neurodegeneration & AD
Reduce Amyloid levels in animal models of AD
Reduce tau biomarker levels (ptau202) in an animal model of tauopathy
PTG-630 is a First-In-Class small molecule for neuroprotection
Praetego's Amadorins Offer a Solution
Praetego’s Amadorins are unique upstream inhibitors of the oxidation. The Amadorins are protective because they attach to redox metal ions to prevent oxidative reactions.
A feature of lead Amadorin PTG-630’s chemical structure allows it to connect to and cap the redox metals. Capping, NOT removing, is what differentiates the Amadorins from chelators. It’s also a strong rationale for an ideal safety profile for a chronic use drug.
Novel Therapeutics to Protect Brain Health
Alzheimer’s Disease
Alzheimer’s disease (AD), the most common form of dementia, 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. 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.
Praetego is committed to developing patient-centric drugs to limit neurodegenerative conditions and diseases; specifically, novel drugs that are potent, well-tolerated, and cost-effective.