The Genetics Podcast

This week on The Genetics Podcast, Patrick is joined by Dr. Cara Altimus, CEO of BD², and Dr. Benjamin Neale, Associate Professor at Harvard Medical School and Massachusetts General Hospital. They discuss how rare variant discovery is opening new routes into bipolar disorder biology, how BD² is combining genetics with longitudinal multimodal data, and how patient priorities are shaping a research model focused on faster diagnosis and more precise treatments.
Show Notes
0:00 Intro to The Genetics Podcast
00:58 Welcome to Cara and Ben
01:57 The origin and aims of BD2 
04:20 Major knowledge gaps in bipolar disorder genetics
06:43 Using genetics and deep phenotyping to map bipolar disorder biology
13:47 Why bipolar disorder genetics needs both scale and deep clinical data
17:32 Finding the most predictive data for bipolar disorder biology and care
19:19 The search for scalable biomarkers in bipolar disorder
21:35 How BD² is building a bridge from discovery to clinical trials
26:48 Why bipolar diagnosis takes years and what patients want research to solve
33:08 How BD² is looking to other programs as inspiration to build a new research model
35:31 What overlapping risk genes reveal across bipolar disorder, schizophrenia, and autism
37:40 How rare variants could de-risk precision psychiatry trials
41:25 How BD² is scaling from early milestones to global funder momentum
45:04 Closing remarks 
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
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BD2

This week on The Genetics Podcast, Patrick is joined by Dr. Angela Bradshaw, Director for Research at Alzheimer Europe and honorary lecturer at the University of Glasgow. Following a series of recent episodes exploring Alzheimer’s disease research, we’re revisiting this conversation to bring in an essential patient advocacy and nonprofit perspective on the field. Patrick and Angela discuss how Alzheimer Europe partners in and supports pan-European dementia research, the heterogeneity of dementia and Alzheimer’s disease, the future of potential new gene therapies, and the critical role advocacy organizations play in ensuring research reflects the needs and priorities of patient communities.
Show Notes
0:00 Intro to The Genetics Podcast
01:27 Welcome to Angela and how she joined Alzheimer Europe
06:06 The biggest priorities and areas of focus for dementia and Alzheimer’s Disease (AD) research
10:10 Biomarkers for dementia and how early in disease development they can be utilized
12:40 The heterogeneity of dementia and AD and current understanding of subtypes and treatment journeys
17:20 The challenges of diagnosis, early identifiers, and the integration of genetics
18:53 Angela’s view on the latest breakthrough therapies
22:50 Partnering in and supporting dementia research efforts across 30+ European countries
29:15 Reimbursement frameworks and shared regulations across different countries
33:40 Angela’s thoughts on the near future of gene therapies for AD and dementia
38:04 Why Angela spent 50 hours travelling the length of Australia by bus
41:26 Closing remarks
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Alzheimer Europe

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This week on The Genetics Podcast, Patrick is joined by Salvador Rico, Chief Medical Officer at Encoded Therapeutics. With Encoded’s Dravet syndrome gene therapy program recently reaching major clinical and regulatory milestones, we’re revisiting this conversation on Salvador’s journey into drug development, his work on gene therapy for X-linked myotubular myopathy, and the fundamental challenges and exciting advances shaping the future of genetic medicine.
Show Notes
0:00 Intro to The Genetics Podcast
01:27 Welcome to Salvador and how he became involved in drug development
11:29 Frustrations and rewards of the genetics field
14:27 Salvador’s study on gene therapy for patients with X-linked myotubular myopathy (XLMTM)
20:13 Risk of liver issues in gene therapy trials and attempts to mitigate them
24:50 Encoded Therapeutics‘ approach to drug discovery and what motivated Salvador to join the team
27:50 Steps towards therapeutic targeting of gene regulatory elements 
30:32 Advantages of different methods for drug delivery 
32:59 DNA- versus RNA-based therapy
 
35:24 Insights from approaches in other fields, including psychiatry
37:03 Considerations for using natural history studies
41:00 Expectations and goals for Encoded Therapeutics’ current and upcoming studies
43:45 Closing remarks
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Encoded Therapeutics

New clinical data

This week on The Genetics Podcast, Patrick is joined by Dr. Vincent Dion, Group Leader at the UK Dementia Research Institute at Cardiff University. They discuss how repeat expansions drive Huntington’s disease and other neurological disorders, why DNA repair can sometimes worsen these mutations over time, and how CRISPR nickase editing could offer a new way to shrink disease-causing repeats rather than simply silence them.
Show Notes
0:00 Intro to The Genetics Podcast
01:00 Welcome to Vincent
01:45 Working on origins-of-life chemistry in Stanley Miller’s lab
03:56 Vincent’s path to genetics 
06:00 How somatic repeat expansion drives Huntington’s disease 
09:40 Therapeutic strategies for Huntington’s disease
15:29 Using gene editing to shrink repeat expansions
18:31 Optimizing CRISPR nickase delivery and expression for repeat expansion editing
25:15 Moving gene editing from academic research toward a first-in-human trial
27:31 Clinical trial challenges for Huntington’s gene therapies and uniQure’s early data
30:47 Epigenetic regulation of repeat instability in neurodegenerative disease
33:14 How basic science breakthroughs like CRISPR become transformative biology tools
34:55 How academic couples navigate the two-body problem when building research careers
39:39 Developing biomarkers to measure whether DNA-targeting therapies are working
42:17 Closing remarks
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This week on The Genetics Podcast, Patrick is joined by Dr. Paul Valdmanis, Associate Professor at the University of Washington. They discuss the impact of APOE4 on risk in Alzheimer’s disease, how long-read sequencing is uncovering hidden genetic variation in Alzheimer’s and ALS, and what rare variants and cryptic splicing can teach us about neurodegeneration.
Show Notes
0:00 Intro to The Genetics Podcast
01:00 Welcome to Paul
01:40 Long-read sequencing and ancestry-specific APOE4 risk in Alzheimer’s disease
04:20 Key findings from Paul’s study on a protective APOE4-linked variant in Alzheimer’s disease
10:58 What rare PSEN1 and PSEN2 variants reveal about Alzheimer’s disease biology
14:38 Disease-specific genetic mechanisms in ALS versus Alzheimer’s
17:14 Precision therapies for neurodegenerative disease
18:35 Choosing therapeutic targets in the neurodegenerative disease cascade
20:21 Landscape of ALS and Alzheimer’s therapies 
23:48 Lessons from liver-directed gene therapy on microRNA toxicity, cancer risk, and brain delivery challenges
29:12 Using long-read sequencing to uncover tandem repeat expansions missed by conventional genomics
33:26 Findings from a study of long-read sequencing on ancient genomes
38:06 Closing remarks
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https://drive.google.com/file/d/1Bp2_wVNSzntTs_zuoizU8bX1dvao4jfj/view?usp=share_link
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APOE study

Ancestry study