The Genetics Podcast

Euan Ashley, Chair of the Department of Medicine at Stanford and co-founder of biotech firms, shares insights from his groundbreaking work in ultra-rapid genome sequencing. He highlights a pivotal case of diagnosing a newborn's cardiac condition in just eight hours. Euan discusses the integration of AI and wearables in preventive medicine, as well as the genetics behind elite athletic performance. Additionally, he explores the ethical considerations of widespread genetic testing and the potential of generative AI in developing novel therapies.

This week on The Genetics Podcast, Patrick is joined by Kent Rogers, Chief Executive Officer at EveryONE Medicines. They discuss Kent’s journey across every side of the desk in the drug discovery space, EveryONE Medicines’ efforts to develop antisense oligonucleotides for ultra-rare diseases, and the need to adapt regulatory models for n-of-1 therapies.Show Notes: 00:00 Intro to The Genetics Podcast00:59 Welcome to Kent and his experiences across every side of the pharma ‘desk’06:00 Challenges of commercialization for ultra-rare disease therapies and the advantage of antisense oligonucleotides (ASOs) 10:28 EveryONE Medicines’ approach to regulatory bodies12:30 Regulatory feedback and expectations from EveryONE Medicines’ platform-based approach to n-of-1 therapies15:47 Differences in regulatory requirements for rare disease across countries 19:53 Insights from being on different sides of the drug development industry22:40 Differences in healthcare systems across countries that can facilitate or impede drug development26:57 Rationale behind focusing on ASOs for treating rare diseases 28:03 Building EveryONE Medicines and Kent’s approach to leadership33:20 Lessons from Kent’s career37:17 Closing remarks Find out moreEveryONE Medicines (https://www.eomeds.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 Matt Burgess, genetic counselor, host of the Demystifying Genetics podcast, and Adjunct Professor at Bay Path University. They discuss the evolution of genetic counseling, ethical challenges in gene therapy, and Matt’s experiences with his podcast.Show Notes: 0:00 Intro to The Genetics Podcast00:59 Welcome to Matt02:09 Matt’s run-ins with Olivia Newton John while working at Austin Hospital in Melbourne04:34 Matt’s background and path to genetic counseling 06:58 The evolution of the field of genetic counseling over time and the role of counselors12:47 Matt’s work on rare disease AP-4 hereditary spastic paraplegia (AP-4-HSP) and the ethical considerations of gene therapy20:22 Balancing the needs and expectations of individuals and families in counseling 23:06 Rebranding negative connotations of the word “counseling”  26:58 Memorable episodes from Matt’s podcast Demystifying Genetics34:31 Differences in genetic counseling and healthcare in the US versus Australia and the UK40:00 Matt’s current work on writing a novel, starting a company called Rosalind Genetics, and being involved in genetic education42:47 The potential and drawbacks of AI models in the context of genetic counseling and information46:46 Closing remarksFind out moreDemystifying Genetics (https://demystifying-genetics.buzzsprout.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 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