Suhail Rasool

Suninflam Ltd, USA

Title: Reversal of Alzheimer’s Disease pathology by TB006 antibody targeting Galectin-3

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Biography

Dr. Suhail Rasool is a Scientific leader currently working as a Senior Vice President/Director in the division of Neurology and Neurodegenerative disease in one of the pharmaceutical company in San Francisco CA USA (Suninflam Inc.). Dr. Suhail has demonstrated expertise across neurodegenerative diseases (AD, FTD, PD, ALS, HD) and inflammatory disease including traumatic brain injury, Epilepsy and stroke. Proven track record in developing diagnostic biomarkers and therapeutic modalities, spanning large molecules, small molecules, cellular therapeutics, and antibodies. These findings led to several years of research and I was recognized by various publications and awards. In addition to research, we were successfully awarded over $3.5M from the NIH to conduct Phase 2A and 2B studies for AD and CAA and the $1.2M Michael J. Fox foundation for Parkinson disease. Recently our two drugs have been approved for clinical trials by FDA one for Alzheimer's disease and another for stroke.

Abstract

Objective:

What leads the oligomerization of A? and is it possible to develop the alternative therapeutic modality for treating AD.

Scope:

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disorder caused by multiple pathogenic factors including Amyloid-? (A?), phospho-Tau, and Apolipoprotein E4 (ApoE4). It is widely accepted that A? intermediate forms (oligomers), rather than monomers or mature fibrils, are more neurotoxic. Galectin-3 (Gal-3) was reported to be involved in A? oligomerization and inflammatory processes

Results:

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. A? deposition and neuroinflammation are reduced in AD mouse brains. Mechanistically, Gal-3 antibody blocked the initiating events in AD (A? aggregates), reduced inflammation and rescued neuronal damage. Furthermore, microhemorrhages, a potential safety liability seen with clinical stage drugs, are reduced. In addition, AD patients dosed with TB006 antibody showed a significant increase in MMSE and lowers Ab42 levels in csf.

Methods used:

Here, we show that Gal-3 promotes oligomerization of A? 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.

Conclusion:

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.