Neuron-Gale
Galectin-3 Inhibitors project tests a small molecule, previously used in peripheral indications, for treating neuroinflammation in an Alzheimer’s mouse model. By blocking Galectin-3, it aims to reduce brain inflammation, with potential in other neurodegenerative diseases. The Galectin-3 Inhibitors project is testing the concept of treating neuroinflammation through a small molecule known to inhibit Galectin-3 in peripheral indications, via direct injection to the brain in the mouse model of Alzheimer’s disease. Galectin-3 is involved in neuroinflammation, thereby the project has a potential to be used in multiple neurodegenerative diseases. Galectin-3 inhibitors are a new class of drugs that could effectively treat neuroinflammation. Galectin-3 has shown to be a critical element in both peripheral as well as neuroinflammation. The project advances how inhibition leads to a resolution of brain inflammation.
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Project
Market Overview
Summary
A glycan-binding protein, galectin-3, has been identified as a key regulator of neuroinflammation and as a target in Alzheimer’s Disease (AD), including the observation that AD patients have significantly increased galectin-3 levels and that galectin-3 knock-out mice have less amyloid plaque deposition and better cognitive features. In this project a highly specific galectin-3 inhibitor will be used 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 patient and societal need with an estimated valueof 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.
Solution
The team has demonstrated the role of galectin-3 in promoting neuroinflammation, Aß plaque deposition and AD, has a wide experience in the discovery of safe, selective, and orally available systemic galectin-3 inhibitors and their development into late clinic trials. The project is focused on the discovery and development of galectin-3 inhibitors with CNS-availability for use in AD therapy.
Current Status
• Glycomimetic galectin-3 weak-binding inhibitors with high MDCK-MDR1 Papp A-B >40×10-6 cm/sec, which 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.
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
We have a competitive edge in our unique galectin-3 inhibitors with far-reaching IP opportunities. 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 inhibitors, the commercial potential for such an inhibitor is large. Inhibitor GB1265 will be chosen based on high affinity for mouse gal3 (Kd 90nM). GB1265 has high solubility allowing for formulation to high concentrations, which is ideal for Alzet pumps and for intraventricular injections.
Market Overview
Summary
A glycan-binding protein, galectin-3, has been identified as a key regulator of neuroinflammation and as a target in Alzheimer’s Disease (AD), including the observation that AD patients have significantly increased galectin-3 levels and that galectin-3 knock-out mice have less amyloid plaque deposition and better cognitive features. In this project a highly specific galectin-3 inhibitor will be used 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 patient and societal need with an estimated valueof 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.
Solution
The team has demonstrated the role of galectin-3 in promoting neuroinflammation, Aß plaque deposition and AD, has a wide experience in the discovery of safe, selective, and orally available systemic galectin-3 inhibitors and their development into late clinic trials. The project is focused on the discovery and development of galectin-3 inhibitors with CNS-availability for use in AD therapy.
Current Status
• Glycomimetic galectin-3 weak-binding inhibitors with high MDCK-MDR1 Papp A-B >40×10-6 cm/sec, which 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.
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
We have a competitive edge in our unique galectin-3 inhibitors with far-reaching IP opportunities. 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 inhibitors, the commercial potential for such an inhibitor is large. Inhibitor GB1265 will be chosen based on high affinity for mouse gal3 (Kd 90nM). GB1265 has high solubility allowing for formulation to high concentrations, which is ideal for Alzet pumps and for intraventricular injections.
Brian Magierski
Co-founder and CEO of 21 Impact Labs and the developer of the soon-to-be-released Xponetiq app for optimizing brain potential. Serial entrepreneur, Co-Founder and CEO/COO of multiple software startups, Brian has successfully raised multiple rounds of VC/PE capital and bought and sold businesses, including the exit of a $340m software startup to a publicly traded company. A passionate advocate for brain health, he is driven by his youngest daughter, who has Down syndrome, to accelerate solutions and cures for Alzheimer’s disease.
Liwaa Chehayeb
9 years of experience in the financial industry, as well as with over 7 years of experience in blockchain and cryptocurrency since 2016. Liwaa has worked on projects of varying scales and companies ranging from crypto startups to the biggest bank in the UAE, First Abu Dhabi Bank (FAB). He is a certified blockchain expert with a master's degree in Crypto & Blockchain from the University of Nicosia (UNIC).
Dr. Maryna Polyakova
Maryna uses neuroimaging, neuropsychological testing, and machine learning to improve early diagnostics of PPA. She works at the Foresight Institute, leading the Neurotech Tree project as they build a new roadmap for the future of neurotechnology. She is also a lecturer at HTW Berlin and the University of Leipzig and Max-Planck Research School, where she teaches an introduction to medicine, with a focus on digital health.
Mark Melnykowycz
Mark has a background in materials science and wearable sensors and gradually became fascinated with UX and product design with brain-computer interfaces. He is excited with the potential to create new science structures using DeSci and LLMs for a sustainable future. Mark styles himself as an artist-engineer, having broad visions inspiration with an understanding of the engineering tools needed to get stuff done in reality.
Yatan Blumenthal Vargas
Venture Builder, Organization Designer, Startup Accelerator, Mindful Leadership Coach, Alzheimer Parent Caretaker, VC Partner. Yatan have been working for 10+ years on helping early-stage startups get from zero to one and for the last few years has gotten interested in brain health for family reasons and wanted to bring more options that give hope and move the needle to the market.
In vivo POC
In vivo POC - Mouse AD model with ascending dose Alzet pump administered readily available Gal3 inhibitor
Analysing brain by ELISA/WB
Analysing brain by ELISA/WB - Inflammation markers, Aß42 levels.
Analysing brain by immunohistochemistry
Plaque load, Microglia analysis (Iba1, Gal3).
Study data analysis
combining the data from the brain analysis to find a clear inhibitory effect on all the descriptors for AD
Emerging role of galectin 3 in neuroinflammation and neurodegeneration
https://journals.lww.com/nrronline/fulltext/2024/09000/emerging_role_of_galectin_3_in_neuroinflammation.32.aspx
The role of galectins in immunity and infection. Nat Rev Immunol, 2023
https://www.nature.com/articles/s41577-022-00829-7
Targeting galectin-3 in inflammatory and fibrotic diseases
https://doi.org/10.1016/j.tips.2023.06.001
Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease
https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c00660
Galectin-3 in Microglia-Mediated Neuroinflammation: Implications for Central Nervous System Diseases
https://www.eurekaselect.com/article/120595
Galectin-3 is elevated in CSF and is associated with Abeta deposits and tau aggregates in brain tissue in Alzheimer's disease
https://link.springer.com/article/10.1007/s00401-022-02469-6
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