Emerging Research Project Aims to Assess the Safety and Efficacy of Genistein in Patients with TTR Amyloidosis 

The CCS-Pfizer ATTR-CM Research Fellowship Award is designed to advance Canadian research in Transthyretin Amyloid Cardiomyopathy (ATTR-CM). This award supports early career Canadian researchers who are committed to developing expertise in diagnosing and treating patients with ATTR-CM. It aims to foster excellence in research and assist researchers in establishing independent careers focused on advancing knowledge and treatment options for ATTR-CM. This year’s award recipient is Dr. Poorna Manappurathu Rameshchandran of the University of Western Ontario. 

As a postdoctoral associate, Dr. Rameshchandran has experience in leveraging induced pluripotent stem cells (iPSCs) for toxicology, drug screening, and disease modeling. In her doctoral research, she used human iPSC-derived hepatocytes as an in vitro drug toxicity screening platform. She also has expertise in assessing the chemosensitivity of natural compounds for treating acute myeloid leukemia (AML). She is the author of 5 publications, including 3 first-author publications, and was selected as a speaker in the Young Investigator Award Session at the 2nd Annual Conference of the Liver Transplantation Society of India. Dr. Rameshchandran’s goal is to become an independent researcher in stem cell biology and drug discovery, and to make a significant impact in cardiovascular research. She aims to utilize her expertise in generating iPSCs and contributing innovative therapeutic approaches for diseases, such as transthyretin amyloid cardiomyopathy. 

Q: What attracted you to this area of research? 

A: This research area fascinates me because Transthyretin (TTR) Amyloidosis is a rare but devastating disease, particularly affecting cardiac function. There are limited treatment options available, and understanding how natural compounds like genistein could modify disease progression is an exciting frontier in cardiology and molecular medicine. Combining inflammation, molecular biology, and clinical cardiology offers a comprehensive way to tackle complex diseases like TTR Amyloidosis. 

Q: How did this project get started? 

A: This project originated from growing evidence that genistein, a soybean derivative, exhibits anti-inflammatory and cardioprotective properties. As TTR Amyloidosis is driven by protein misfolding and inflammation, we hypothesized that genistein could potentially stabilize disease progression. The idea evolved from preclinical studies and small molecule research, which showed promising results in stabilizing TTR tetramers and mitigating inflammation. 

Q: What stage are you at in your research? 

A: We are in the enrollment phase, aiming to recruit 40 participants for this study. Preparations for baseline assessments, including blood sample collection and echocardiographic measurements, are underway. 

Q: When do you expect this study to be completed? 

A: The study will take about 18 months, including time for enrolling participants, treatment, and follow-up. We expect to finish all patient follow-ups within this period 

Q: Can you walk us through what your project entails? 

A: The project aims to assess the safety and efficacy of genistein in patients with TTR Amyloidosis. We will administer increasing doses of genistein over 12 weeks, followed by a six-week washout. Blood samples will be collected at various points to measure inflammatory biomarkers, while echocardiography will assess cardiac function. Exercise capacity will also be evaluated using a 6-minute walk test. The primary focus is on changes in inflammatory markers, with secondary endpoints including cardiac function and exercise tolerance improvements. 

Q: What knowledge gap will this fill? 

A: This study addresses two significant gaps. First, it will provide data on the safety and tolerability of genistein in humans with TTR Amyloidosis, which has been largely unexplored. Second, it seeks to clarify the role of inflammation in the progression of amyloid-related cardiac dysfunction and whether targeting inflammation can improve clinical outcomes. 

Q: What is the value of this research? 

A: The value of this research lies in its potential to uncover a new therapeutic option for TTR Amyloidosis, a condition that currently has limited treatment avenues. This study on genistein, a natural compound, could lead to new treatments for managing TTR Amyloidosis and other heart conditions related to inflammation. 

Q: How will you measure the impact of your research? 

A: The impact will be measured by assessing changes in inflammatory and cardiometabolic biomarkers, cardiac function (via echocardiography), and exercise capacity. If genistein demonstrates efficacy in improving these parameters, it could pave the way for larger trials and potential inclusion in therapeutic guidelines for TTR Amyloidosis. 

Q: What does this fellowship award mean to you, personally? 

A: This fellowship is a significant milestone in my career. It provides me with the resources and platform to pursue a project that could potentially change the therapeutic landscape for a rare but serious disease. Personally, it reinforces my commitment to translational research, where discoveries in the lab can be brought to the bedside to improve patient outcomes. 

Q: Tell us about your research team. 

A: Our research team is multidisciplinary, combining expertise in cardiology, molecular biology, and clinical trials. We work closely with experts in the required fields to ensure the study is complete and well-rounded.