Identification of transthyretin tetramer kinetic stabilizers to inhibit retinol-dependent RBP4-TTR interaction: Novel therapeutics for macular degeneration and transthyretin amyloidosis

Title : Identification of transthyretin tetramer kinetic stabilizers to inhibit retinol-dependent RBP4-TTR interaction: Novel therapeutics for macular degeneration and transthyretin amyloidosis

Abstract:

The interaction between retinol-binding protein 4 (RBP4) and transthyretin (TTR) is implicated in the pathogenesis of diseases such as macular degeneration and transthyretin amyloidosis. Our study identifies novel kinetic stabilizers of the TTR tetramer, offering a therapeutic strategy to inhibit this critical interaction. Through a robust screening of chemical libraries, we isolated compounds that effectively stabilize TTR tetramers. These stabilizers were shown to disrupt the RBP4-TTR interaction, a novel approach in managing these diseases. Our analyses confirm the efficacy of these stabilizers in reducing TTR aggregation. This research opens avenues for developing treatments for macular degeneration, transthyretin amyloidosis, and their related comorbidities, potentially impacting patient care for these age-related conditions.

Audience Take-Away: 

• Understanding of TTR Amyloidosis and Macular Degeneration: The audience will gain a comprehensive overview of these diseases, their impact on health, and the role of the RBP4-TTR interaction in their pathogenesis
• Innovative Therapeutic Approaches: Insight into the identification and role of Transthyretin (TTR) tetramer kinetic stabilizers in disrupting RBP4-TTR interactions, a novel therapeutic strategy
• Scientific Methodology and Discovery: Insights into the methodology used for identifying these stabilizers, including chemical screening and various assays
• Clinical Implications: The efficacy and potential therapeutic impact of these stabilizers in treating TTR amyloidosis and macular degeneration
• Future Research Directions: Future directions for research and potential clinical applications of these finding

Biography:

Dr. Srinivasan Jayakumar is an accomplished Postdoctoral Research Associate currently affiliated with the Rensselaer Polytechnic Institute in New York, USA. He specializes in Synthetic Organic and Medicinal Chemistry, bringing over eight years of detailed research experience which includes five years of Industrial experience at Syngene International Pvt Ltd, India. Dr. Jayakumar's educational background includes a Ph.D. in Organic Chemistry from National Tsing Hua University, Taiwan, and a Master’s in chemistry from Guru Nanak College, University of Madras, India.

In 2020, he transitioned to the U.S., undertaking a postdoctoral research position at Albany College of Pharmacy and Health Sciences, NY,  and is currently engaged with Rensselaer Polytechnic Institute in Troy, NY. Dr. Jayakumar's notable research focuses on developing GlyT2 inhibitors for the treatment of neuropathic pain and RBP4 antagonists for the treatment of age-related macular degeneration, Transthyretin Amyloidosis, and their Common Age-related comorbidities.

In addition to his research work, Dr. Jayakumar actively contributes to the scientific community. He serves on the editorial boards of several international chemistry journals and has a strong track record as a journal reviewer. His publications span a range of topics in medicinal and synthetic organic chemistry, reflecting his broad expertise and commitment to advancing the field.