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.
Prof. Tomas Deierbrog
Tomas Deierborg is a Professor at Lund University in the south of Sweden, where he is head of the Experimental Neuroinflammation Lab. He is also head of the Department of Experimental Medical Science and a member of the strong neuroscience research environment MultiPark at Lund University, studying neurodegenerative diseases from molecules to rehabilitation. He began his scientific career in brain ischemia and became interested in microglia in the context of neurogenesis, discovering how a stroke or a brain lesion could affect neural stem cell proliferation and differentiation by injury-activated microglia. He became interested in the microglia protein galectin-3, which was exclusively expressed in strongly activated microglia, e.g., close to an ischemic lesion or around a plaque in the brain of Alzheimer’s disease individuals.
Prof. Ulf Nilsson
Ulf conducts research into molecular recognition, Galectin chemistry and biology, the inhibition of bacterial symporters and the chemistry of neural interfaces. He obtained his PhD at Lund University 1995 working with oligosaccharide synthesis under the supervision of professor Göran Magnusson. He did post-doctoral studies 1995-1997 at University of Alberta, Canada, with professor Ole Hindsgaul developing methods for combinatorial carbohydrate chemistry. He initiated his independent research career at Lund University 1998 as an assistant professor. Nilsson was promoted to associate professor/senior lecturer in 2001 and full professor in 2009.
Fredrik Zetterberg
Fredrik is a consultant at Biozet AB and additionally works as VP head of medicinal chemistry at Aqilion AB. He worked as VP of medicinal Chemistry at Galecto Biotech, a small biotech company focused on the development of galectin inhibitors for the treatment of fibrosis and cancer. In that role he managed a preclinical department consisting of Medicinal Chemistry, in vitro and in vivo ADME and galectin specific in vitro pharmacology with the major aim at delivering new clinical candidates but also supported the clinical portfolio. He obtained his Master of science degree from Gothenburg University 1994, PhD from Uppsala University 1998 working with Pr. David Tanner and Pr. Pher G. Andersson and then moved on to work for AstraZeneca. At AstraZeneca he contributed to different roles and to several clinical candidates in the cardiovascular and metabolic field.
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.
Peter Groenen
Industry executive with deep expertise in pharmaceutical R&D, specializing in translational science and biomarker integration in drug discovery and development. Led cross-functional teams advancing biomarker strategies and bridging preclinical and clinical research. Experienced in driving projects from early research to late-stage development, collaborating with academia, industry, and regulatory bodies to accelerate therapeutic innovation. Skilled in data-driven decision-making, alliance management, and strategic problem-solving to navigate scientific and operational challenges.
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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