This week on The Genetics Podcast, Patrick is joined by Dr. Graham Dempsey, CEO and co-founder of Quiver Bioscience. They discuss Graham’s path into neuroscience and biotech, how Quiver is building genetically validated programs in pain and neurodevelopmental disorders, and what recent advances in RNA-based therapies could mean for the future of neurological disease.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Graham
01:29 The motivations and mission driving Quiver Bioscience
04:34 Quiver’s approach to targeting the brain for neurological disease
06:58 Nav1.7 as a lead pain program and the mechanisms of pain signaling
12:11 Patient population and unmet need in chronic pain
13:37 The Dup15q neurodevelopmental program and recent clinical progress
17:29 How the company chooses which diseases to pursue and why genetically validated pain and epilepsy programs lead the pipeline
20:10 Modeling pain in a dish and how cellular electrophysiology reveals disease and drug effects
27:42 Lessons from building a biotech company
29:53 Today’s biotech climate and why Graham is optimistic
31:56 Emerging delivery technologies that could unlock the next wave of oligonucleotide therapies
33:51 How molecular shuttles cross the blood–brain barrier and the advantage of a dual target approach
37:05 Graham’s path from aspiring sports medicine doctor to building light-based platforms in neuroscience
40:15 Graham’s early exposure to biotech leadership and a formative encounter with Roy Vagelos
42:09 Closing remarks
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Find out more:
Quiver Bioscience (https://www.quiverbioscience.com/)
This week on The Genetics Podcast, Patrick is joined by Dr. Arabella Bouzigues, Coordinator of the Genetic Frontotemporal Dementia Initiative (GENFI) and postdoctoral researcher. They discuss the scale and structure of GENFI as a global collaboration and what longitudinal data is revealing about genetics and biomarkers in frontotemporal dementia.
Show Notes:
0:00 Intro to The Genetics Podcast
01:00 Welcome to Arabella
01:30 Background and structure of the Genetic Frontotemporal Initiative (GENFI) consortium
02:48 Scale of the GENFI cohort and the breadth of longitudinal data collected
06:06 Clinical signs and progression of frontotemporal dementia (FTD)
10:08 How genetic variants map onto different clinical forms of frontotemporal dementia
12:11 Biomarkers in genetic FTD and the challenge of separating neurodegeneration from lifelong brain differences
19:36 Mutation-specific cortical microstructure patterns in FTD and what MRI reveals at the earliest stages
23:04 Why combining genetics imaging fluid and digital biomarkers is essential for early detection and trials in FTD
25:39 How the GENFI consortium is run across more than 50 sites worldwide
30:42 How urgency and unmet need drive strong collaboration in the FTD community
33:11 Promising developments in FTD therapeutics
36:39 Closing remarks
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
Find out more:
GENFI (https://www.genfi.org/)
This week on The Genetics Podcast, Patrick is joined by Dr. Krishna Aragam, Section Head of Cardiovascular Genomics and Precision Medicine at the Cleveland Clinic. They discuss Krishna’s early experiences in population research and how they shaped his approach to genetics, the major discoveries transforming cardiovascular genomics from monogenic to polygenic risk, and how new insights into heart failure and population-specific variants are redefining the future of clinical care.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Krishna
01:40 How a gap year in India deepened Krishna’s interest in health and population genomics
06:16 Key advances that reshaped cardiovascular genomics from rare variants to polygenic risk
09:18 Where cardiovascular genomics stands today across coronary disease, cardiomyopathies, and arrhythmias
14:25 Factors that make heart failure challenging for genomics
17:32 How monogenic variants and polygenic load shape risk in dilated cardiomyopathy
23:03 What genetics reveals about the roots of heart failure and why precise phenotypes matter
26:12 Using genetic risk to guide earlier treatment and prevent progression to heart failure
30:37 Subclinical markers and imaging strategies to track progression toward heart failure
32:04 Key research findings on an ancestry-specific genetic driver of dilated cardiomyopathy
41:21 Genetic signals highlighting the role of inflammation in coronary artery disease
43:11 Building a clinical genomics engine that connects discovery to cardiovascular care
47:14 Closing remarks
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
Find out more:
Genetic variants underlying DCM: https://pmc.ncbi.nlm.nih.gov/articles/PMC11631752/
Ancestry-specific CD36 study: https://www.nature.com/articles/s41588-025-02372-2
Summary:
This week on The Genetics Podcast, Patrick is joined by Lisa Gurry, Chief Business Officer of GeneDx. They discuss her path from two decades at Microsoft to leading one of the most influential genomics companies, GeneDx’s mission to deliver the fastest rare disease diagnoses, and how large-scale data, newborn screening, and AI are shaping the future of precision medicine.
Show Notes:
0:00 Intro to The Genetics Podcast
01:00 Welcome to Lisa and her career path leading to joining GeneDx
03:27 The core components of GeneDx and how they drive early rare disease diagnosis
06:18 Insights from early genomic newborn screening pilots
11:37 The clinical impact and economic benefits of newborn genomic screening
14:27 How GeneDx combines data, AI, and clinical expertise to improve genomic interpretation
17:44 A vision for a lifelong genomic passport and how it could guide care across every stage of life
20:42 How GeneDx Infinity is unlocking new therapeutic possibilities in genetically linked autism
22:48 How advocacy communities guide patient identification and connect families to opportunities
26:00 Lessons from 23 years at Microsoft that Lisa now applies to leading GeneDx
30:39 How Truveta emerged from the COVID crisis to build a shared-data platform for population-scale health insights
32:13 What excites Lisa most about leading GeneDx and where she sees the biggest opportunities ahead
34:59 Closing remarks
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 Dr. Jeffrey Chamberlain, Professor at the University of Washington School of Medicine, co-founder of Kinea Bio, and Director of the Muscular Dystrophy Cooperative Research Center of Seattle. They discuss the early breakthroughs that revealed the structure and function of the dystrophin gene, how those insights led to the creation of micro-dystrophin and systemic AAV delivery in Duchenne, and the major scientific and clinical challenges the field must now solve.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Jeffrey
01:33 Early discovery of the dystrophin gene and how it shaped Duchenne muscular dystrophy (DMD) research
09:07 Efforts to map dystrophin and develop practical diagnostic techniques
12:04 How research in Jeffrey’s lab gradually led to the creation of micro-dystrophin
20:15 How micro-dystrophin and AAV delivery converged into a viable systemic gene therapy strategy
27:23 Current successes and safety challenges in systemic AAV gene therapy for neuromuscular disease
34:44 Prospects and limitations of gene editing for Duchenne and emerging alternatives to AAV micro-dystrophin
44:57 Closing remarks
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
Summary:
This week on The Genetics Podcast, Patrick is joined by Dr. Rachel Salzman, CEO of Armatus Bio. They discuss the promise of vectorized RNAi for autosomal dominant diseases, the key scientific and clinical hurdles in gene therapy, and Rachel’s lessons from two decades in the field.
Show Notes:
0:00 Intro to The Genetics Podcast
01:00 Welcome to Rachel
01:35 Background of Armatus Bio and the mechanism behind its vectorized RNAi platform
05:31 Advantages of vectorized RNAi over conventional RNAi approaches
08:07 How microRNAs work and how engineered versions enable highly specific gene silencing
10:28 Current preclinical progress at Armatus and next steps toward first-in-human trials
14:06 Lessons on making smart risk decisions in rare disease drug development
17:26 Reflections on two decades of progress, setbacks, and realities in gene therapy
22:07 Hemophilia as a case study in gene therapy missteps and overlooked patient and market realities
25:21 Challenges around product purity and the need for financial innovation
29:23 Why AAV purity is so difficult to achieve and where pre-competitive collaboration could drive improvement
33:32 Rachel’s path from veterinary medicine to gene therapy through a family genetic diagnosis
35:58 Founding the Stop ALD Foundation and advancing lentiviral gene therapy into first-in-human use
39:58 The future potential of vectorized RNAi
42:00 Closing remarks
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
Summary:
This week on The Genetics Podcast, Patrick is joined by Slavé Petrovski, Vice President of the Center for Genomics Research at AstraZeneca. They discuss how AstraZeneca is scaling population genomics through massive biobank collaborations, developing AI models for early disease prediction, and pioneering sustainable “green” algorithms to reduce the environmental footprint of large-scale genomic research.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Slavé
02:09 Slavé’s career path from business information systems to genomics
04:33 How Slavé decided to move from academia to industry
07:52 Scaling and diversifying biobank partnerships to unlock new genetic insights
12:29 Translating biobank data into predictive and preventive medicine
15:14 Discovering protective genetic variants through global biobank studies
19:13 Leveraging population genetics to identify and validate protective drug targets
23:52 Developing an AI tool (MILTON) for integrating multi-omic and clinical data for early disease prediction
28:12 Redefining clinical trials in a presymptomatic and predictive medicine era
30:49 AstraZeneca’s efforts to make large-scale genomics computing sustainable through green algorithm innovation
39:05 AstraZeneca’s open science strategy and global impact of its shared genomics tools
42:10 Fostering critical thinking and avoiding groupthink in large-scale genomics research
45:30 Looking ahead to the next decade of genomics and precision healthcare
50:01 Closing remarks
Find out more
MILTON (https://www.astrazeneca.com/r-d/our-technologies/machine-learning-drug-discovery.html)
PheWAS Portal (https://azphewas.com/)
Upcoming webcast with deep dive into MILTON & PheWAS (https://www.nature.com/articles/d44224-025-00033-7)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Dr. Ellen Reisinger, Professor and group leader at the University of Tübingen. They discuss her journey into hearing loss research, why otoferlin has become a leading target for gene therapy, and the emerging science shaping the next generation of treatments.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Ellen
01:52 Ellen’s career path that coincidentally led to her work on otoferlin-related hearing loss
03:22 Mechanism and advantages of the dual adenoassociated virus (AAV) system
05:35 The genetic landscape of early-onset hearing loss and why otoferlin stands out
07:42 Why otoferlin-related deafness is an ideal target for postnatal gene therapy development
09:53 Potential next gene therapy targets beyond otoferlin and associated challenges
13:13 Carrier and newborn screening as approaches to preventing hereditary hearing loss
14:37 How far the field is from prenatal gene therapy and why it remains unlikely in the near term
16:07 Exploring gene-agnostic and protective approaches to prevent or slow hearing loss
18:22 How genetics and environment interact in age-related hearing loss
20:00 Current research focus of Ellen’s group on degenerative hearing loss genes and uncovering cell death mechanisms
22:05 Using mouse models and human organoids to study hearing loss mechanisms
23:42 Emerging gene editing approaches
25:20 Ellen’s research journey from biochemistry to leading gene therapy research in hearing loss
27:54 Unanswered questions about how inner hair cells release neurotransmitters
29:21 Comparing outcomes of gene therapy and cochlear implants for hearing restoration and differences across languages
34:20 Closing remarks
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
Summary:
This week on The Genetics Podcast, Patrick is joined by BridgeBio’s Ananth Sridhar, Chief Operating Officer of Cardiorenal Programs, and Sun-Gou Ji, Vice President of Computational Genomics. They discuss the hub-and-spoke model for de-risking and accelerating rare disease drug development, the role of human genetics in target discovery, lessons from their autosomal dominant hypocalcemia type 1 (ADH1) program, and how portfolio design and predictive genomics are shaping the future of precision medicine.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Ananth & Sun-Gou
01:57 How BridgeBio’s hub-and-spoke model de-risks and accelerates rare disease drug development
06:45 How programs move from the hub to the spokes in target discovery and development
09:10 Translating a target into a therapy for autosomal dominant hypocalcemia type 1 (ADH1)
12:28 Challenges in ADH1 drug development and using population genetics to identify patients with gain-of-function variants
18:08 Under-diagnosis and incomplete penetrance in rare disease and quantifying genetic versus phenotypic prevalence
20:52 Balancing first-in-class innovation with risk management in rare disease drug development
24:24 Evaluating rare disease programs using risk-adjusted net present value (NPV) instead of peak sales
27:20 Key factors that can make rare disease programs faster and cheaper to develop, and why modality agnosticism is important
32:00 Sun-Gou’s experience in computational genetics and building data-driven infrastructure for discovery
36:44 Ananth’s lessons from Regeneron and applying patient-centered principles to rare disease drug development
39:00 Sun-Gou on the power of newborn sequencing and personal lessons from early diagnosis
43:36 Ananth’s views on making predictive medicine more personal and human-centered
44:51 Closing remarks
Find out more
BridgeBio (https://bridgebio.com/unlocking-rare-diseases-medicine)
Hub-and-spoke model (https://www.youtube.com/watch?v=gRURL49QsX4)
ADH1 publication (https://www.cell.com/ajhg/fulltext/S0002-9297(25)00244-7)
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
Summary:
This week on The Genetics Podcast, Patrick is joined by Justin Porcano, co-founder and Executive Director of Save Sight Now. They discuss how his daughter’s diagnosis with Usher syndrome type 1B (USH1B) inspired the founding of Save Sight Now, the organization’s efforts to accelerate research and overcome barriers in gene therapy, and the innovative gene delivery methods and therapeutic approaches currently in development.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Justin
01:39 How Justin’s daughter’s Usher syndrome diagnosis (USH1B) led to the founding of Safe Sight Now and a mission to accelerate research
05:23 Biggest hurdles to therapeutic development for USH1B
08:36 Progress in the research with new animal models and advances in clinical endpoint development
10:25 How Justin applied design thinking and AI to rapidly learn rare disease science
12:38 Advances in gene delivery approaches for USH1B
15:45 Therapeutic intervention windows in USH1B with early treatment for hearing loss and later options for addressing vestibular and visual impairments
18:32 Save Sight Now’s plans for the next phase of clinical translation and sustainable growth
20:50 Why Justin decided to establish Save Sight Now as an independent nonprofit
22:27 The need for stronger collaboration between patient organizations and biotech companies
25:50 Building global collaborations to expand Save Sight Now’s reach
28:00 How the community can support Save Sight Now’s mission and upcoming fundraising gala
28:59 Closing remarks
Find out more
Save Sight Now (https://www.savesightnow.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
Summary:
This week on The Genetics Podcast, recorded live at ASHG 2025, Patrick is joined by Heidi Rehm, Chief Genomics Officer at MGH’s Center for Genomic Medicine and Co-director at the Broad Institute, and Slavé Petrovski, Vice President of AstraZeneca's Centre for Genomics Research. They discuss the rapid progress of large-scale genomics, the barriers to integrating genetic data into healthcare and drug development, and how open collaboration, global data sharing, and a focus on equity are driving more inclusive and impactful genomic discovery.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Heidi and Slavé
02:01 Slavé’s role at AstraZeneca and work in genomics-driven R&D
03:24 Heidi’s work at the Broad Institute bridging clinical genomics, rare disease research, and global data-sharing initiatives
04:12 Heidi on breaking a Guinness world record for rapid neonatal ICU (NICU) genomics and the shift to open data sharing
06:32 Slavé on how large-scale, multimodal human data is transforming genomics research
08:10 Heidi’s initiatives to integrate genomics into routine care at hospitals and with primary care physicians
11:47 Integrating genomics into clinical trials and healthcare, and enabling global discovery through AstraZeneca’s open data portal
15:34 Breaking down legal and logistical barriers to genomic data sharing and centering the patient voice
18:40 AstraZeneca’s large-scale plasma proteome study and machine learning models predicting disease onset years before diagnosis
21:44 Emerging omics tools advancing rare disease diagnosis
24:19 The value and pitfalls of AI in genomics today
28:54 Advancing health equity in genomics through data sharing, diverse recruitment, and global collaboration
33:40 Progress and challenges in next-generation genetic therapies
37:15 Reflections and advice for the next generation entering genomics and data-driven medicine
40:44 Audience Q&A
51:44 Closing remarks
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Chris Hopkins, CEO of Glafabra Therapeutics. They discuss how Glafabra is advancing a next-generation cell therapy for Fabry disease, the differences between gene therapy modalities, and the future of cell and gene therapy innovation.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Chris
01:28 Overview of Fabry disease and reviving a promising shelved gene therapy
03:12 Limitations of current Fabry disease treatments versus Glafabra Therapeutics’ approach
05:19 How autologous cell therapy avoids an immune response
06:43 Comparing this cell therapy approach to that of Casgevy for sickle cell disease
11:28 Expanding Glafabra’s platform to other lysosomal storage disorders through enzyme cross-correction
13:47 Comparing autologous cell therapy and AAV in Fabry
17:02 Path to clinical development and funding strategy for Glafabra’s lead program
19:33 Cost efficiency and trial design advantages of an orphan drug approach
21:19 Considerations around comparator groups for Glafabra’s therapy
24:11 Underdiagnosis and hidden prevalence of rare diseases
25:53 Other innovations Chris is excited about and expectations for the future of cell and gene therapy
31:56 How Chris invented a technique to safely “milk” venomous cone snails
37:00 Closing remarks and advice for scientists taking the leap from academia to entrepreneurship
Find out more
Glafabra Therapeutics (https://www.glafabra.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
Summary:
This week on The Genetics Podcast, Patrick Short takes a solo deep dive into the current state of gene therapy ahead of next week’s live recording at ASHG. He explores the promise and limitations of adeno-associated virus (AAV) delivery, examples of gene therapies for neuromuscular diseases, and the challenges of balancing safety, cost, and commercial viability in rare diseases.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Episode overview
02:50 Definition and scope of gene therapy
04:50 Gene therapy delivery via adeno-associated virus (AAV) and associated challenges and advantages
06:40 AAV-based gene therapy and other advanced therapies in spinal muscular atrophy (SMA)
10:29 Recent safety concerns around Sarepta Therapeutics’ AAV-based gene therapy for Duchenne muscular dystrophy (DMD)
19:30 Commercial viability challenges for rare disease gene therapy
24:26 Risk-benefit analysis of gene therapy for rare diseases
28:33 Considerations for optimizing AAV design and delivery routes
31:26 Alternative approaches for delivery using viral and non-viral methods
36:09 The future of AAV gene therapy
41:42 Closing remarks
Find out more
Update on Sarepta Therapeutics’ gene therapy for DMD (https://www.fiercepharma.com/pharma/sarepta-shares-more-elevidys-safety-data-response-patient-group-fda-petition)
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
Summary:
This week on The Genetics Podcast, Patrick is joined by Andy Singleton, Program Lead of the Global Parkinson’s Genetics Program (GP2), and Sonya Dumanis, COO of the Coalition for Aligning Science. They discuss the creation of GP2, how the initiative is closing representation gaps in genetics, and building global infrastructure and capacity for research.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Sonya and Andy
01:50 Aims and overview of the Global Parkinson’s Genetics Program (GP2)
03:15 The Aligning Science Across Parkinson’s (ASAP) initiative and how it led to the creation of GP2
04:37 Gaps in Parkinson’s genetics that inspired the creation of GP2
07:21 Closing the global representation gap in Parkinson’s genetics
08:37 ASAP’s model for long-term resources and adaptive funding
11:18 How GP2 overcame pandemic disruptions and data-sharing challenges to grow global capacity
15:01 Using harmonized data to compare Parkinson’s with other neurological diseases
17:02 Expanding GP2’s scope while keeping Parkinson’s at the core
18:42 Using genetics to guide targeted Parkinson’s therapeutics
21:37 Early biomarkers beyond genetics including proteomics and alpha-synuclein seed amplification assay (SAA) to guide therapy timing
23:01 Adapting GP2 to incorporate new discoveries and build capacity for functional and longitudinal studies
26:54 Insights from GBA variants into gene expression and Parkinson’s risk biology
28:24 How GP2’s open access data can be used to power clinical trials and advance drug development
31:37 Lessons from GP2 on building sustainable global collaboration and capacity that can be applied across disease areas
36:10 Navigating global differences in genetic testing access, regulation, and return of results across the GP2 network
38:29 Building coalitions between philanthropy, nonprofits, and industry to sustain large-scale initiatives
41:09 The story behind the GP2 tattoos and the team spirit that fuels the program
42:23 Closing remarks
Find out more
GP2 (https://gp2.org/)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Wanda Smith, founder of CureGRN. They discuss Wanda’s journey from caring for her mother to driving FTD research, the discovery of progranulin and development of new therapies, the diagnostic odyssey and need for earlier genetic testing, and how the CureGRN community is expanding support and awareness worldwide.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Wanda
02:18 Wanda’s journey into frontotemporal dementia (FTD) research from being a caregiver to establishing a brain bank
06:31 Shifting focus after the discovery of progranulin (GRN) and accelerating FTD research through collaboration
08:23 How GRN haploinsufficiency drives FTD and what it means for therapy
11:57 Implication of progranulin in neurodegenerative diseases and therapies now in clinical trials
13:33 Why earlier genetic testing and diagnosis are critical for families with GRN mutations
15:31 Barriers behind the diagnostic odyssey and limited access to genetic testing
17:03 Moving from symptom-based diagnosis to early diagnosis with biomarkers
19:50 Expanding CureGRN’s reach through global collaboration
21:14 Raising awareness to drive FTD research
22:44 Overcoming stigma and shame to encourage trial participation in FTD
24:41 Navigating family conversations about FTD with compassion and meeting people where they are
26:39 Providing multiple pathways for families to access support, education, and community
28:35 Insights into the future of FTD and addressing the gaps preventing progress in care and diagnosis
30:58 The importance of genetic testing and community resources in FTD
33:23 The role of younger gene carriers in shaping early detection, prevention, and long-term care in FTD
37:00 Closing remarks
Find out more
CureGRN (https://www.curegrn.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
This week on The Genetics Podcast, Patrick is joined by Terry Pirovolakis, CEO and Founder of Elpida Therapeutics. They discuss Terry’s journey to create a life-saving gene therapy for his son, the founding of Elpida Therapeutics to bring hope to families with ultra-rare diseases, and the challenges of scaling therapies that aren’t commercially viable.
Show Notes:
0:00 Intro to The Genetics Podcast
00:58 Welcome to Terry
01:24 The beginning of Terry’s gene therapy journey after his son Michael was diagnosed with SPG50
03:24 Learning the biotech industry and building a gene therapy team
05:17 Terry’s experience with learning about gene therapy without a scientific background
06:42 The process of building a gene therapy in under three years during the COVID-19 pandemic
09:30 Fundraising through community support and major donors
11:06 Expanding access of Michael’s gene therapy to children all over the world
12:32 The creation of Elpida Therapeutics to develop non-commercially viable therapies and adapting to a challenging funding landscape
15:24 Insight into cost, accessibility, and the role of endpoints and manufacturing
20:06 Learning from safety events as gene therapy scales and the importance of considering the risk/reward ratio in rare disease
23:24 Landscape of precision therapeutics available today beyond AAV vectors
27:09 Designing trials at Elpida to demonstrate efficacy in ultra-rare disease
29:24 Adapting meaningful endpoints to disease progression and FDA flexibility
34:02 Background of Priority Review Vouchers and the negative impact of its non-renewal on rare disease funding
37:48 Finding optimism in rare disease family initiatives and gene therapy successes, and the future of advanced therapeutics
41:07 How to support the rare disease community and families
44:16 Closing remarks
Find out more
Elpida Therapeutics (https://www.elpidatx.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 Samuli Ripatti, Director of the Institute for Molecular Medicine Finland (FIMM), Vice Director at HiLIFE, and Professor of Biometry at the University of Helsinki. They discuss Samuli’s research on lipid and cardiovascular genetics, how polygenic risk scores are moving into clinical care, and the power of the FinnGen biobank.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Samuli
01:48 Samuli’s path from statistics to genetics at the beginning of a new era
03:09 Remembering Leena Peltonen and the Human Genetics Summer School
05:46 Samuli’s research in lipid and cardiovascular genetics and the power of collaboration
09:14 Integrating polygenic risk scores into cardiovascular and breast cancer care
14:52 Using medication history in FinnGen to uncover cardiometabolic genetics and predict treatment patterns
18:50 The future of polygenic risk scores in predicting prognosis and guiding treatment
21:21 The confounding effect of treatment in genetic studies
23:14 Overview of FinnGen and its impact on genetics and drug discovery
27:04 The next 5 years in proteomics and molecular profiling to move beyond associations
29:56 Using polygenic risk scores in clinical trials
31:41 Future directions, from refining phenotypes in large biobanks to piloting clinical applications of polygenic risk scores
34:04 Scaling population biobanks versus deep phenotyping and why the future requires both
35:29 Closing remarks
Find out more
Genetic predictors of lifelong medication-use patterns in cardiometabolic diseases (https://www.nature.com/articles/s41591-022-02122-5)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Jonathan Marchini, Head of Statistical Genetics and Machine Learning at the Regeneron Genetics Center. They discuss Jonathan’s pioneering role in developing computational methods from the HapMap era through to today, how those innovations underpin large-scale imputation and analysis, and why exomes with imputation remain more powerful than whole genomes for discovery at Regeneron.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Jonathan
01:47 Jonathan’s career path from teaching in rural Tanzania to genomics research at Oxford
04:43 Lessons from the HapMap era and the birth of imputation
08:30 Ongoing challenges with data sharing and usable tools
10:30 Handling massive genetic datasets at Regeneron and developing new computational methods to scale
15:26 Key discoveries from the million-exome paper
18:04 Pushing computational limits in meta-analysis
19:50 Polygenic risk scores in the clinic and their role in trial design
23:38 Why Regeneron prioritizes exomes with imputation over whole genomes and what that means for discovery
27:58 Where AI truly adds value in genomics and where simpler models still win
32:27 Interpreting rare variants, the promise of protein models, and why better phenotyping is key
35:31 Closing remarks and opportunities at Regeneron
Find out more
Regeneron Genetics Center (https://www.regeneron.com/science/genetics-center)
Million exome paper (https://www.nature.com/articles/s41586-024-07556-0)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Max Bronstein, CEO of Aviva Strategies. They discuss the shifting regulatory and political landscape shaping biotech, the realities of today’s drug development process, and why new incentives and flexible trial pathways are critical to advancing rare and ultra-rare disease therapies.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Max
01:51 Regulatory shifts and FDA challenges under the new administration
05:40 Overview of the regulatory process for therapeutic development and the push for patient-centered trials
11:26 Challenges in drug development from regulatory gaps to shifting FDA priorities
15:45 Unprecedented government turnover and its impact on biotech industry stability
18:32 Status and significance of the pediatric priority review voucher program for rare and ultra-rare disease development
22:02 How Congress uses “must-pass bills” to advance or block health policies
25:17 Max’s role in creating Advanced Research Projects Agency for Health (ARPA-H) to drive high-risk innovation
30:02 How ARPA-H is funded
31:21 Adapting science policy to politics
33:35 Breakthroughs in rare disease therapies and the policy frameworks needed to ensure access
37:15 Lessons from the Orphan Drug Act and why new incentives are needed to make ultra-rare disease drug development viable
39:23 The push for flexible rare disease trial pathways and the disconnect between FDA rhetoric and practice
43:26 Closing remarks and a call to connect for patient organizations and rare disease parents
Find out more
Aviva Strategies (https://www.avivastrategies.com/)
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
This week on The Genetics Podcast, Patrick is joined by Richard Wilson, Senior Vice President, Primary Focus Lead of Genetic Regulation at Astellas. They discuss where the gene therapy field stands today, diving into successes, persistent barriers, regulatory considerations, manufacturing strategies, and other reflections on important approaches to precision medicine drug development.
Show Notes:
0:00 Intro to The Genetics Podcast
00:59 Welcome to Richard
01:33 Current wins and challenges in gene therapy
07:13 The need for more open non-competitive data sharing and a clearer pathway towards reimbursement and incentivization
11:15 Building post-approval systems into the genomic medicine lifecycle
14:47 Rethinking evidence standards in rare disease trials, and the global push for regulatory and reimbursement alignment
20:28 Genetic medicine breakthroughs in central nervous system diseases
22:25 The challenges of starting clinical development with an end in mind
24:34 The need for careful analysis around endpoints, vector design, and delivery approaches
29:33 Navigating regulatory hurdles when making mid-program changes to vectors or payloads
31:16 Strategies for enhancing scalability and quality of gene therapy manufacturing
36:05 Exploring other delivery methods beyond AAV
39:32 Getting ready for the Timmerman Traverse and raising nearly $1M for Life Science Cares
43:48 A call to refocus on patients, partnership, and purpose in uncertain times
45:55 Closing remarks
Find out more
Astellas (https://www.astellas.com/)
Timmerman Traverse fundraising for Life Science Cares (https://timmermantraverse.blackbaud-sites.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