Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder caused by multiple pathogenic factors including Amyloid-β (Aβ), phospho-Tau, and Apolipoprotein E4 (ApoE4). It is widely accepted that Aβ intermediate forms (oilgomers), rather than monomers or mature fibrils, are more neurotoxic. Galectin-3 (Gal-3) was reported to be involved in Aβ oligomerization and inflammatory processes. Here, we show that Gal-3 promotes oligomerization of Aβ and other pathogenic factors, and TB006, a monoclonal antibody targeting Gal-3, acts as a possible treatment for AD  by degrading neurotoxic oligomers and reducing inflammation. In vitro, Gal-3 intrinsically and selectively promotes, while mTB001 and TB006 degrade, oligomerization of only the pathogenic protein forms like Ab42, phospho-Tau and ApoE4. Gal-3 enhances, while mTB001 blocks, Ab42-induced microglia activation and neuronal death. In three mouse models of AD, cognitive deficits are strongly attenuated after just two weeks of mTB001 treatment. Aβ deposition and neuroinflammation are reduced in AD mouse brains. Mechanistically, Gal-3 antibody blocked the initiating events in AD (Aβ aggregates), reduced inflammation and rescued neuronal damage. Furthermore, microhemorrhages, a potential safety liability seen with clinical stage drugs, are reduced. Pre-clinical studies show that TB006 is an efficacious therapeutic entity through degradation of toxic oligomers and blocking or even reversing AD progression.  Clinically, TB006 has shown a superior safety profile without any drug-related adverse events in a healthy volunteer trial.

Suhail Rasool is the Director of Neurodegenerative Diseases Research at Truebinding Inc. He focuses on developing diagnostic biomarkers and therapies for Alzheimer’s and other neurodegenerative diseases. Over the past five years, his key contributions include characterizing molecular probes for diagnosing Alzheimer's, Parkinson's, prion disease, cerebral amyloid angiopathy, and traumatic brain injury using the retina. He has also advanced a novel Alzheimer's diagnostic candidate and explored fluorescent probes for amyloid visualization. In late 2021, the FDA cleared an IND application for TB006, a lead product candidate for Alzheimer’s treatment