TGR63 as a potential drug candidate for the treatment of Alzheimer’s Disease

Dr. Sourav Samanta’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. The author, Dr. Sourav Samanta, was born on May 1st, 1991, at Natibpur, West Bengal, India. After his initial schooling at Natibpur Bhudeb Vidyalaya, he obtained his Bachelor’s degree in Chemistry in 2013 from Bangabasi College under Calcutta University, India. He obtained his Master Degree in Chemistry in 2015 from the Department of Chemistry, Indian Institute of Technology Guwahati (IIT Guwahati), Assam, India. He joined the New Chemistry Unit (NCU), Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India, for the PhD program in August 2015 under the guidance of Prof. T. Govindaraju. He received his Doctor of Philosophy (PhD) degree in Chemistry from JNCASR in February 2021. Currently, he is appointed as a postdoctoral research associate (PRA) under the supervision of Prof. T. Govindaraju at JNCASR. Here, Sourav talks his first author wort titled ‘Naphthalene Monoimide Derivative Ameliorates Amyloid Burden and Cognitive Decline in a Transgenic Mouse Model of Alzheimer’s Disease’ publishd in Adv Therap (2021).

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How would you explain your paper’s key results to the non-scientific community?

Alzheimer’s disease (AD) is a major neurological disorder constituting 70-80% of all dementia cases. Unfortunately, there are no effective medications to cure AD. Our goal was to develop drug candidates to cure or halt AD progression. Our perseverant efforts of over 10 years resulted in the discovery of a potent drug candidate TGR63, which significantly reduce the build-up of toxic protein aggregates in the AD brain, thereby rescuing neurons (brain cells) from degeneration. The TGR63 treated mice showed amelioration of learning, memory, and cognitive and overall behavioral deficiencies. The long-term administration of TGR63 through intraperitoneal (IP) injection is non-toxic to animals. These key attributes make TGR63 is a potential drug candidate for the treatment of AD.

What are the possible consequences of these findings for your research area?

Currently, the available medications offer just temporary relief, and no approved drugs are available that directly act on the AD mechanisms. Consequently, there is an unmet need to develop promising drug candidates to halt or cure AD. The multifaceted amyloid toxicity attributed to the multifactorial nature of AD has been the major hurdle in the development of effective therapeutic agents. Our strategy (design, synthesis, and identification) to develop novel drug molecules targeting core disease mechanisms to tackle AD led to discovery of potential drug candidate TGR63, which is ready for clinical studies.

What was the exciting moment (eureka moment) during your research?

Success in research is nothing but a sum of several interesting results that always excite us. We were enthusiastic about this molecule (TGR63) after analyzing its unique interactions with the target Amyloid Beta (Aβ) peptide, a key contributor to multifaceted AD toxicity. Finally, the eureka moment was when we found that TGR63 treated AD animals showed reduction of amyloid burden accompanied by reversal of cognitive decline.

What do you hope to do next?

We are preparing for clinical validation of TGR63 through a pharmaceutical company.

Where do you seek scientific inspiration?

The mental illnesses that have a significant impact on our society and economy have been largely neglected. There is an unmet need to bring awareness in our society about mental health and age-related diseases and advanced research to tackle these chronic illnesses. We are actively involved in understanding the pathological routes of various neuronal disorders, specifically Alzheimer’s disease, to develop unique therapeutics. Further, the clinical failure of several drug candidates over the last decades have compelled us to work on drug discovery for Alzheimer’s disease. These efforts have led to the discovery of TGR63 through a distinct design strategy that targets core disease mechanisms.

How do you intend to help Indian science improve?

We are thankful to the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), the Department of Science & Technology (DST), Science and Engineering Research Board (SERB). Government of India, for providing funding and infrastructure. I would like to contribute to Indian science through focused advanced research in the area related to human health, especially to tackle neurological diseases.

Reference
Samanta, S., Rajasekhar, K., Ramesh,M., Murugan, N.A., Alam, S., Shah, D.,Clement, J.P. and Govindaraju, T.(2021), Naphthalene MonoimideDerivative Ameliorates AmyloidBurden and Cognitive Decline in aTransgenic Mouse Model ofAlzheimer’s Disease. Adv. Therap., 4:2000225. https://doi.org/10.1002/adtp.202000225

Email: sourav@jncasr.ac.in

Prof. T. Govindaraju lab: http://www.jncasr.ac.in/tgraju/

Co-Founder and Director, VNIR Biotechnologies Pvt. Ltd.

Edited by: Anjali Mahilkar (Copy Editor, Volunteer, Biopatrika)

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