Summary

A glycan-binding protein, galectin-3, has been identified as a key regulator of neuroinflammation and postulated as a target for treating Alzheimer’s Disease (AD), supported by the observations that AD patients have significantly increased galectin-3 levels and that galectin-3 knock-out mice have less amyloid plaque deposition and better cognitive functions. In this project a highly potent and specific galectin-3, non brain penetrable inhibitor will be directly infused in the brains in an in vivo AD mouse model to monitor effects of galectin-3 inhibition and potentially validate galectin-3 as a target for pharmacological intervention.

Problem

AD (and Parkinson’s) represents a large unmet medical and societal need with an estimated value of over $30 billion by 2033 (Yahoo finance). Today ~55 million people are affected, and the number is expected to increase. The economic burden is around $1.3 trillion. Current treatments, antibodies or small molecules, are not effective and at best disease-slowing and with side effects. Currently there are no potent galectin-3 inhibitors that pass the blood brain barrier.

Solution

The project aims to test a Galectin-3 inhibitor in a Proof-of-Concept study to mitigate neuroinflammation, Aß plaque deposition in a mouse model of Alzheimer’s disease. An orally available systemic galectin-3 inhibitor for peripheral indications will be infused directly into the brain for a period of four weeks to test the research hypothesis.

Current Status

- Glycomimetic galectin-3 weak-binding inhibitors with high MDCK-MDR1 Papp A-B >40×10-6 cm/sec, which suggests that CNS-available inhibitors can be discovered.

- A soluble glycomimetic galectin-3 high affinity and selective tool inhibitor selected for in vivo Proof of Concept (PoC) in a mouse AD model.

- The tool inhibitor will be chosen based on high affinity for mouse galectin-3, solubility allowing for formulation to high concentrations, which is ideal for Alzet pumps and for intraventricular injections.

- Provided that the proposed mouse in vivo PoC with the tool compound robustly confirms galectin-3 as a drug target in AD, a medicinal chemistry development would be the next step.

Commercial potential

The AD therapeutic market is valued in the tens of billions of dollars annually. A disease-modifying galectin-3 inhibitor with compelling efficacy and safety profile could attain blockbuster drug status, especially if positioned for early-stage or pre-symptomatic AD populations.

Given that the proposed in vivo PoC here confirms galectin-3 as a target and that a subsequent DDD campaign identifies optimal CNS-available galectin-3 inhibitor, the IP will be filed.

Galectin-3 is a novel target in AD. First-mover advantage could be significant if clinical trials show meaningful cognitive or biomarker benefit, particularly with oral, small molecule candidates. This would allow capturing large market share, licensing, partnering, or acquisition interest from major pharma companies.

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