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Business Discussion
Our Butyrylcholinesterase Inhibitor (BChE-I) Portfolio in Neurodegenerative Diseases

BChE is a promising target for treating advanced stages of Alzheimer's disease (AD). Its prevalence increases in severe AD, making it suitable for mid- to severe AD patients. Additionally, BChE is linked to key AD hallmarks, such as amyloidogenesis. Exploring hybrid drugs that target BChE alongside other therapeutic objectives holds potential for anti-Alzheimer's treatments.

Developing the Next-Gen of highly potent and selective BChE Inhibitors with the potential to revolutionize symptomatic treatments for late-stage Alzheimer's disease.

Alzheimer’s Disease: An overview

  • A prevalent form of Dementia characterized by cognitive and memory decline in aging individuals.

  • Involves Amyloid beta (Aβ) plaques and neurofibrillary tangles.

  • The cholinergic hypothesis suggests that reduced acetylcholine in the brain contributes to AD;

  • Notably, 3 out of the 7 AD-approved drugs are Cholinesterase Inhibitors (ChEI).

 

BChE: The New Frontier

  • BChE levels can increase by 40-90% in the AD brain.

  • This increase predominantly occurs in the temporal cortex and hippocampus, areas most affected by AD.

  • In pivotal brain areas such as the human hippocampus and amygdala, 10% of ChE-positive neurons contain BChE.

  • High levels of BChE are found in neuronal plaques in AD.

  • Both AChE and BChE amplify the activity of the toxic Beta-Amyloid peptide in tissue culture.

  • BChE may be involved in the transformation of diffuse Beta-Amyloid into compact, neuritic plaques.

  • There is evidence of a link between the K variant of BChE, ApoE4 and the incidence of some forms of AD.

  • Selective BChE inhibitors can increase ACh levels in the rat cortex without affects on AChE.

  • Selective BuChE inhibitors can improve learning in elderly rats.

Potential benefits of BChE inhibition

  • Likely to improve outcomes in clinical therapy of AD, especially in later stages when BChE levels increase.

  • Selective BuChE inhibition is potentially advantageous because it may circumvent the classical cholinergic toxicity that is a common side effect of AChE inhibition.

  • Potential applications extend beyond AD, including Parkinson’s disease (PD), dementia with Lewy bodies, and combating drug abuse, like heroin.

 

Overview of Lead Compounds PE01 and PE02

Crafted through Pharmaeconomica's cutting-edge in-house computational framework, PE01 and PE02 stand as testimonies to our commitment to explore the vast chemical space, utilizing high-performance computing and AI-driven insights, that exhibit potential as BChE inhibitors.

Efficacy & Potential:

  • Selective Targeting: Achieved potent inhibition with low micromolar IC50 values against equine BChE with up to 98% inhibition. Using equine BChE models, given their similarity to human BChE, offers insights into potential human therapeutic applications.

  • High Specificity: Displayed minimal inhibition against AChE, underscoring their specificity for BChE over AChE.

  • Optimized for Brain Delivery: High permeability in the PAMPA-BBB model indicates promising brain bioavailability, a critical factor for neurodegenerative disease treatments.

  • Potential for Enhanced Efficacy: These leads have inherent characteristics allowing significant optimization, signifying the potential for even more targeted and efficient results.

Partner with Us

 

Unlock the Future of Alzheimer's Treatment with PE01 & PE02:

  • Innovative Collaborative R&D: Partner with us in refining and optimizing the potential of these leads. Exploit our expertise and capabilities to achieve shared success.

  • Exclusive Opportunities: Get early access to groundbreaking research and data surrounding our portfolio, and stay at the forefront of neurodegenerative treatment innovations.

  • A Partnership with Purpose: Join our mission to revolutionize treatments for Alzheimer's and other neurodegenerative diseases. Let's combine our strengths to redefine the therapeutic frontier for Alzheimer's and related conditions.

Reach out to us today for exclusive collaborative opportunities and be part of the next big leap in neurodegenerative disease treatment.

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