The Genetics Podcast Sano Genetics

In this episode of The Genetics Podcast, we're joined by Dimitar Tonev, an experienced drug development consultant specialising in Hepatology and Virology. Tune in to discuss the recent reclassification of Non-alcoholic Steatohepatitis (NASH) to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), and the complexities of identifying treatments for this condition.

Dimitar sheds light on the pioneering role of non-invasive biomarkers and comments on the potential impacts of the Maestro study. Join us as we dive into the world of liver disease and drug development, touching upon the breakthroughs, challenges, and ethical considerations of clinical trials.

For anyone interested in liver health innovations and the future of hepatology research, this episode is a must-listen.

In this episode of The Genetics Podcast, we welcome Dr. Konstantinos Lazaridis, the Executive Director of the Center for Individualized Medicine at the Mayo Clinic. Tune in to learn about the impacts of genomics and individualised medicine on rare liver diseases and advanced cancers . Discover how the Mayo Clinic actively uses genomic testing, precision medicine, and environmental interventions to improve patient outcomes.

In this episode, Patrick welcomes Caroline Wright, a leading expert in genomic medicine and Professor of Genomic Medicine at Exeter University. Listen in as they delve into the world of rare diseases, discussing the challenges in diagnosis, uses of population cohorts and, the potential of newborn screening. Caroline shares her excitement about new technologies in genomics and emphasises the importance of data sharing. Discover the significance of genetic variants and the need for cautious interpretation.

In this episode, Patrick welcomes J. Warren Huff, CEO and Chairman of Reata Pharmaceuticals. Reata is known for innovating small-molecule therapies for severe and life-threatening diseases. Listen in as Warren walks us through their approach of partnering with Universities to find scientific discoveries that could become the next generation of therapies, and Reata’s recent success developing a groundbreaking new treatment for Friedreich’s Ataxia (FA), thanks to close collaboration with patient organizations and novel use of natural history data to accelerate their clinical development.

0:00 The beginnings of Reata

2:40 Partnering with universities for breakthroughs in research

5:30 Implications of cancer prevention research on chronic diseases

11:40 Potential concerns in medical ethics and Big Pharma when developing groundbreaking treatments

13:20 Research on NRF2 and its role in treating Friedreich’s Ataxia, a genetic mitochondrial disease that leads to motor neuron decline

18:00 What is a natural history study, and how was it used in Reata’s FA clinical development?

22:50 The potential for clinical grade wearable devices

23:35 Determining clinical endpoints in clinical trials

26:00 The FDA’s approval process for rare disease treatments

32:40 Potential for expanding newborn screening programs

36:00 The generalizability of NRF2-based research to other inflammatory diseases and diseases related to mitochondrial malfunction

39:40 What is Type 3 Diabetes?

40:30 Warren’s career start as a lawyer and his journey to biotech

43:00 Searching for provocative biology

46:20 Major targets for the HSP program

48:30 Closing remarks and lessons in resiliency

Join Patrick Short and Professor Clare Turnbull, Professor in Translational Cancer Genetics at the Institute of Cancer Research, as they discuss polygenic risk scores and their application in healthcare. Delve into the complexities of predicting disease, the challenges of screening programs, and the potential impact of integrating genomics into healthcare systems. Discover the limitations and potential of polygenic risk scores and gain valuable insights into the future of personalized medicine.

0:00 Intro

1:00 Clare’s path to becoming a clinical geneticist and her research in uncovering genetic links to cancer

3:20 How do Polygenic Risk Scores help to predict disease, particularly breast cancer?

10:00 The influence of environmental and genetic effects on breast cancer presentation

11:30 Next clinical steps after determining genetic risk for breast cancer

17:30 How effective and accurate are polygenic risk scores in predicting various types of cancer, given the potential for false positives or negatives?

25:00 The potential for integrating genetic screenings and polygenic risk scores into early cancer diagnosis

27:20 How do monogenic risk scores like BRCA 1 and 2 fit into the paradigm of cancer research?

31:30 Using both monogenic and polygenic to explain population prevalence of disease

35:00 Integration of genomics and genetic screenings into the UK healthcare system

40:30 What comes after the genetic test? What is the use in identifying risk for a disease if nothing is subsequently done to prevent it?

44:50 Clare’s upcoming work in remodeling NHS systems for evidence protocols and clinical use of genetic tests

46:50 Closing remarks

In this episode, Patrick is joined by Dr. Mike Severino, CEO of Tessera Therapeutics and CEO-Partner of Flagship Pioneering. Join us as Mike walks us through Tessera’s approach to treating genetic diseases by rewriting bases, exons, or even whole genes with a novel approach called Gene Writing.

0:00 Intro

1:00 What prompted you to join Flagship Pioneering?

3:32 How is Flagship able to innovate and invent novel therapies in ways that Big Pharma companies may find difficult?

5:00 Introduction to gene writing and the role of Tessera Therapeutics

8:22 The current limitations and challenges of gene writing

10:22 Gene knockouts vs gene writing – which is more useful for genetic therapies?

12:30 Reasons why the liver the most commonly targeted organ for gene therapies

19:00 Lipid Nanoparticles and their role in gene writing

22:45 How do you guide mobile genetic elements to write genes in the intended location?

25:20 Development of gene writing technology since 2018

28:15 The implications of gene writing for diseases like PKU, Alpha-1 antitrypsin deficiency, sickle cell disease, and cancer

34:00 Next steps on the way to clinical trials

36:46 Using genomics and computational biology to guide measurable outcomes in drug discovery and development

40:15 Using gene writing to address rare developmental diseases

43:32 Closing remarks