The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Salvador Rico, Chief Medical Officer at Encoded Therapeutics. They discuss Salvador’s journey into drug development, his work on gene therapy for X-linked myotubular myopathy, and fundamental challenges and exciting advances in the genetics field.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Salvador and how he became involved in drug development11:01 Frustrations and rewards of the genetics field13:59 Salvador’s study on gene therapy for patients with X-linked myotubular myopathy (XLMTM)19:46 Risk of liver issues in gene therapy trials and attempts to mitigate them24:22 Encoded Therapeutics‘ approach to drug discovery and what motivated Salvador to join the team27:22 Steps towards therapeutic targeting of gene regulatory elements 30:04 Advantages of different methods for drug delivery 32:31 DNA- versus RNA-based therapy 34:56 Insights from approaches in other fields, including psychiatry36:35 Considerations for using natural history studies40:32 Expectations and goals for Encoded Therapeutics’ current and upcoming studies43:17 Closing remarksFind out moreEncoded Therapeutics (https://encoded.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Leeland Ekstrom, CEO and co-founder of Nashville Bio. They discuss how Leeland went from being a consultant on a project for Vanderbilt University to a co-founder of a start-up and the unique aspects of NashBio’s clinical and genetic database.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Leeland and the origin story of Nashville Bio05:13 Process of setting up NashBio’s genome resource with 250K individuals11:52 How different pharmaceutical companies responded to NashBio’s database and its unique advantages compared to others17:50 Key priorities for applications of the resource beyond target discovery20:19 The process of selecting additional gaps that NashBio’s services can fill versus letting others fill them25:02 Advantages at Vanderbilt Medical Center that facilitated the project and how it can be replicated at other centers30:32 Immediate and long-term impacts of current NIH funding cuts on biotech and academia36:43 NashBio’s current major focuses and future goals39:20 Closing remarksFind out moreNashBio (https://nashbio.com/)Press release: Alliance for Genomic Discovery completes 250,000 whole genomes to accelerate drug discovery (https://www.illumina.com/company/news-center/press-releases/press-release-details.html?newsid=b4b0c901-f8a2-4802-a4ef-b81167e24cfe) Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Sharon Terry, President & CEO of Genetic Alliance. They discuss how Sharon established a layperson-led biobank, her long-term work on rare diseases and patient advocacy, and her program to bring genetic technology to patients in low- to middle-income countries.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Sharon and a discussion of the personal experience with rare disease that started her journey03:47 Reasons why Sharon decided to establish the first layperson-led biobank05:34 Challenges with setting up the biobank infrastructure07:00 Balancing financial factors in a non-profit organization 09:30 Recent patterns and future insight into rare disease drug discovery framework and regulation15:32 Barriers to widespread collaboration and cooperation in rare disease research, and why it should be approached from a public health perspective18:12 Background and experiences from the iHope Genetic Health program in low- to middle-income countries24:44 Sharon’s perspective on current challenges with the Genetic Information Non-discrimination Act28:49 Sharon’s lessons learned in her patient advocacy and policy work, and her hopes for future legislation 33:04 Sharon’s hopes for improved access to genetic testing and treatment for children in underserved communities34:34 How Sharon learned about rare diseases and genetics as a “homeschooling mom without a degree”37:54 Insights into how elements of spirituality can support advocacy work40:18 Closing remarksFind out moreGenetic Alliance (https://geneticalliance.org/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

John Lepore, physician-scientist and CEO of ProFound Therapeutics, shares insights on expanding the human proteome to discover novel drug targets. He discusses the creation of the ProFoundry atlas and its role in integrating genomic data. The conversation highlights innovative drug discovery methods, collaboration with Pfizer for obesity research, and strategies for biotech firms to engage with pharma partners. John’s background as a cardiologist informs his approach, emphasizing the connection between scientific research and patient care.

This week on The Genetics Podcast, Patrick is joined by Raghib Ali, CEO, CMO, and Principal Investigator of Our Future Health UK. As a clinical epidemiologist with a passion for reducing health inequalities, Raghib offers fresh insights into the priorities, challenges, and transformative impact of the groundbreaking genomics initiative, Our Future Health. Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to Raghib and background on Our Future Health (OFH)03:57 Diseases that are a priority for OFH or are likely to benefit from its impact06:07 Challenges and opportunities for implementing change in the National Health Service (NHS), a partner of OFH, based on study findings09:20 Factors that contributed to the rapid recruitment of participants to OFH14:12 Efforts to ensure diversity of OFH participants and facilitate accessibility for all16:35 Why OFH chose to use arrays for genomic profiling18:57 Navigating the obstacles and opportunities in public and private partners22:28 Strengths and weaknesses of the medical record system in the UK 25:54 Efforts to rapidly provide results from OFH and integrating other datasets and techniques in the future28:43 Raghib’s unique educational and training journey 31:49 The importance of evaluating components beyond genetics for a full picture of health33:28 Aims and findings of the first prospective cohort study in the UAE35:26 The potential contribution of epigenetic inheritance to disease risk 37:43 How Raghib overcame adversity early in life40:56 Closing remarks Find out moreOur Future Health (https://ourfuturehealth.org.uk/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, we’re celebrating Rare Disease Day with a very special episode. Patrick is joined by clinical nephrologist Anthony Bleyer and geneticist Stan Kmoch to discuss how their decade-long international collaboration has uncovered genetic mutations in families with rare inherited kidney diseases – including Patrick’s.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Anthony and Stan02:05 The origin story for Anthony and Stan’s long-distance collaboration06:55 Stan’s background in metabolic disorders and sequencing techniques11:09 Common genetic culprits and barriers to identifying mutations that cause kidney disease14:01 Background and findings from Anthony and Stan’s ApoA4 study23:54 Potential therapeutic avenues based on the ApoA4 study26:49 Current and future focuses for characterizing diseases in families30:42 Working with collaborators internationally to access large databases and registries33:05 Innovative transplant methods, including genetically-modified pig kidneys 36:36 Closing remarks and a heartfelt thank you to researchers and families driving rare disease researchFind out more Latest study: https://doi.org/10.1016/j.kint.2023.11.021Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Michelle Werner, CEO at Alltrna and CEO/Partner at Flagship Pioneering. They discuss Alltrna’s promising findings from its first preclinical study on using tRNA to rescue stop codon disease, the strategic use of basket trials, and more!Show Notes: 0:00 Intro to The Genetics Podcast01:00 Welcome to Michelle02:13 Overview of Alltrna’s aims and the advantages of using tRNA to tackle stop codon disease5:27 Using basket trials for genetic diseases08:03 Highlights from Alltrna’s first preclinical study using tRNA to restore protein production to clinically meaningful levels in methylmalonic acidemia (MMA) and phenylketonuria (PKU)14:02 Considerations in delivery techniques and Alltrna’s use of nanoparticles19:22 Stability of tRNA and how engineered tRNAs are recognized in vivo 23:12 Strategic design of basket trials and diseases that are covered26:16 Adaptive trial design in the rare genetic disease setting28:15 Michelle’s experience with regulatory organizations on new approaches to trial design32:14 Insights from spearheading Alltrna and Flagship Pioneering’s innovative approaches 37:26 Michelle’s lessons from working in big pharma versus a small biotech start-up40:50 Closing remarks and a call for collaboratorsFind out more Alltrna (https://www.alltrna.com/)Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

On this week’s episode of The Genetics Podcast, we’re joined by Jocelynn Pearl, Director of Cancer Cell Therapy at the TAM Center, host of the Lady Scientist Podcast and Co-Founder of LabDAO. Patrick and Jocelynn discuss her move to Mexico to help accelerate the development of new cancer therapies, harnessing the power and potential of decentralized science, and overcoming sky-high gene therapy costs to increase accessibility for patients.Show Notes: 0:00Intro to The Genetics Podcast01:00Welcome to Jocelynn02:03 Jocelynn’s past work at The Institute for Systems Biology 04:55 How Jocelynn approached her transition to biotech from the world of academia10:14 Exploring decentralized science, including how it works and Jocelynn’s involvement to date15:54 What a Decentralized Autonomous Organisation (DAO) is and how this type of organizational structure supports scientific development22:45 The “fast grant” surge and other non-traditional funding methods28:00 Hosting the Lady Scientist Podcast and some of Jocelynn’s favorite moments32:43 Jocelynn’s move to Mexico to serve as Director of Cancer Cell Therapy at the TAM Center36:12 The biggest differences between building out drug development programs in Mexico and the US38:31 Regulatory differences between countries in the context of stem cell therapies42:48 The advantages for cancer therapeutic development in Jocelynn’s current environment46:20Driving down the costs of gene therapies and the impact on accessibility  48:09 Closing remarksFind out moreLabDAO:https://www.lab.bio/ Please considerrating and reviewing us on your chosen podcast listening platform!https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj 

Summary:  This week on The Genetics Podcast, Patrick is joined by Eric Adler, Chief Medical Officer and Head of Research at Lexeo Therapeutics and Professor of Medicine at University of California San Diego. Eric shares his experience with genetic cardiomyopathy and his work on gene therapy for Danon disease, drawing from both clinical and research perspectives. Additionally, he explores the evolution of the field and the broader challenges faced by cardiovascular patients. Show Notes:  0:00 Intro to The Genetics Podcast 01:00 Welcome to Eric and his efforts in cardiomyopathy at the bench and bedside 03:32 How modeling genetic diseases using pluripotent stem cells lead Eric to studying Danon disease  04:50 Pivoting from basic to translational research using adeno-associated viruses (AAV)-based gene therapy 07:58 Uncovering genetic cardiomyopathies that were misdiagnosed as idiopathic cardiomyopathy 09:55 Treatment, screening, and penetrance of Danon disease 12:30 Recent successes and remaining challenges in cardiovascular disease 19:47 Battling distrust in the medical profession 21:55 Preventative therapy using APOE2 for patients at risk of early Alzheimer’s   25:15 Motivations behind and advantages of Eric’s patient-centered approach to therapeutics 27:24 Balancing regulatory requirements for protocols versus patient needs 29:49 The importance of committed clinical partners for successful trial execution 36:08 Eric’s passion for cooking and how he won a cooking competition 39:02 Closing remarks and Lexeo Therapeutics’ aims for 2025 Find out more Lexeo Therapeutics (https://www.lexeotx.com/) Please consider rating and reviewing us on your chosen podcast listening platform!  https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link

This week on The Genetics Podcast, Patrick is joined by Versha Pleasant, Clinical Assistant Professor in the Department of Obstetrics and Gynecology, University of Michigan and Director of the Cancer Genetics and Breast Health Clinic at Von Voigtlander Women’s Hospital. They discuss ongoing disparities in healthcare, in particular why black women in the US have a 40% higher chance of dying from breast cancer than white women, the impact of the US Educate Act on equality, diversity and inclusion education, and much more. 00:00:00 – Intro to The Genetics Podcast 00:01:52 – Welcome to Versha 00:03:22 – How black women have a 40% higher chance of mortality from breast cancer than white women, and the biggest drivers of this disparity 00:07:09 – Multifaceted approaches to addressing disparities 00:09:10 – Racial health duplicity and increasing access to genetic testing and mammography for black women 00:13:51 – The challenges of using precision medicine to stratify risk in black communities and historical harms in US medical research 00:14:29 – How to design for inclusive studies that effectively represent communities of colour 00:16:13 – Considering universal genetic testing and counseling for black women 00:21:24 – The logistics of making universal testing a reality, and the importance of community education and trust building 00:27:18 – What Versha is focused on next and the big topics she wants to tackle 00:33:24 – The role of community education and diversifying modes of communication for knowledge sharing 00:34:36 – Versha’s perspectives on the US Educate Act and the impact it could have on what doctors of the future are taught 00:40:52 – Versha’s advice to people who would like to pursue a similar career in medicine 00:43:28 – Where Patrick sees genetics evolving in the next ten years and his vision for the future of The Genetics Podcast 00:47:39 – Closing remarks Find out more Universal Genetic Counseling and Testing for Black Women: A Risk-Stratified Approach to Addressing Breast Cancer Disparities: https://www.clinical-breast-cancer.com/article/S1526-8209(24)00338-0/fulltext  Please consider rating and reviewing us on your chosen podcast listening platform! https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link