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)

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 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)

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 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/)

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 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

This week on The Genetics Podcast, we celebrate our 200th episode with a look back at some of the earliest episodes, particularly ones that foresaw major trends or went on to spark real-world impact. These include Eric Topol’s early predictions about AI in healthcare, Laurence Reid’s vision for gene therapy in hearing loss, Sir Rory Collins on the potential impact of the UK Biobank, Daphne Koller on uniting biology and machine learning, and Vineeta Agarwala on harnessing large datasets for drug discovery. Patrick adds updates and reflections on how these bold ideas have shaped the genomics and biotech landscape.

Show Notes:

0:00 Intro to The Genetics Podcast

00:59 Overview of episode content and guests featured

01:47 Eric Topol predicts the role of AI in healthcare in 2019

05:58 Patrick’s reflections on AI’s progress today and future potential

06:57 Laurence Reid outlines Decibel Therapeutics’ gene therapy plans for otoferlin-related hearing loss

10:58 Patrick’s updates on Decibel’s success and acquisition by Regeneron

11:44 Sir Rory Collins on the creation and vision of the UK Biobank

18:20 Patrick on the lasting impact of open science and the UK Biobank

19:10 Daphne Koller on building insitro to fuse biology and machine learning

24:30 Patrick on the future of large-language models in biology

25:55 Vineeta Agarwala on investing in large datasets for drug discovery

32:24 Patrick on applying multi-omic data to rare disease research

32:52 Closing remarks

Find out more

The Genetics Podcast is now on Instagram! Follow us for clips from recent episodes and release announcements (https://www.instagram.com/thegeneticspodcast/).

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 Xin Jin, Associate Professor in the Department of Neuroscience at The Scripps Research Institute. They discuss how in vivo Perturb-seq enables scalable and high-resolution modeling of neurogenetic disorders like autism, how introducing mutations directly into living mouse brains reveals cell-type vulnerabilities and convergent pathways, and why this approach could transform therapeutic development by identifying shared mechanisms across diverse genetic mutations.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:58 Welcome to Xin 

01:52 Overview of in vivo Perturb-seq

05:10 Identifying de novo variants in autism spectrum disorder

09:00 Using perturbations to map how autism-linked mutations affect specific brain cell types

13:04 Applying Perturb-seq to other brain diseases

14:30 In vivo versus in vitro models and extending genetic screening approaches beyond the brain

18:44 Using in vivo models to trace variant effects, rank gene drivers, and uncover therapeutic pathways

22:35 Conservation of genes between mouse and human in the context of neurodevelopmental disease modeling 

24:21 Impact of genetic discoveries on drug development by convergence onto common pathways 

27:22 Xin’s early interest in science through her grandfather’s work in plant taxonomy and botany

29:48 Xin’s path from China to MIT and how early research shaped her scientific mindset

31:58 Reflections on AI’s rapid progress and limits in biology, and the need for new models 

37:21 Closing remarks

Find out more

• Jin lab (https://www.jin.scripps.edu/)

• In vivo Perturb-seq explainer video (https://vimeo.com/549737357)

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 Benny Sorensen, CEO of Hemab Therapeutics. They discuss how Hemab is reimagining clotting therapies by centering patient voices, how persistence and being “unreasonable” led to their first program, and the value of their multi-modality and collaborative approach.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:59 Welcome to Benny

01:49 Reimagining blood clotting therapies by listening to lived experience and embracing the biotech revolution

04:27 How persistence and patient voices sparked Hemab’s first drug development program

07:13 Overview of Glanzmann Thrombasthenia (GT) and Hemab’s antibody-based approach

10:09 Evolution of hemophilia treatment and neglected blood clotting disorders

14:18 Genetic and gender considerations around bleeding disorders

17:41 Hemab’s range of therapeutic modalities and the value of collaboration 

21:00 Why deep domain expertise drives Hemab’s strategy and success

22:55 Lessons from the drug development process

24:16 Global insights into gender bias, health inequality, and bleeding disorder care

26:46 Upcoming milestones at Hemab 

29:52 Lessons from running natural history studies to capture the patient experience

33:25 Redefining the patient journey through data

34:40 How Benny’s experience at Alnylam Therapeutics shaped his “unreasonable” leadership

38:16 Reflections on being a father and a CEO 

40:38 Closing remarks and Benny’s commitment to thoughtful drug development

Find out more

• Hemab Therapeutics (https://www.hemab.com/)

• Hemab trial register (https://shorturl.at/8AAQN) 

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 Heiko Runz, medical geneticist and VP of Neuroscience at insitro. They discuss Heiko’s path into therapeutic genetics, how collaboration and data integration across biobanks led to his discovery of a protective variant for age-related macular degeneration, and the role of cell-based models in drug discovery.

Show Notes: 

0:00 Intro to The Genetics Podcast

00:58 Welcome to Heiko

01:41 Heiko’s career path and how he became interested in medical genetics and therapeutic development

05:49 Connecting the dots across biobanks for genetic discovery

08:23 Heiko’s discovery of a potential gene target for age-related macular degeneration

15:29 The challenge of biobank recontact and why it’s essential for follow-up studies

18:57 The opportunity for smaller companies to follow up on large-scale genomic discoveries

23:00 Advances in cell-based models for neuroscience drug discovery

24:40 Heiko’s role in the development of tofersen for SOD1 ALS 

28:50 Targeting TDP-43 in ALS through large-scale cell-based phenotyping and drug discovery

30:36 Using cell-based phenotypes to functionally test disease mechanisms and validate variants

33:58 The potential of AI for refining phenotypes and generating drug hypotheses

36:47 Heiko’s advice to early career professionals interested in the field of genetics and drug discovery

38:26 Closing remarks 

Find out more

• insitro (https://www.insitro.com), study on CFHR5 (https://www.nature.com/articles/s41467-025-61193-3)

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