エピソード

  • First in human gene editing: a new era for IMD therapies

    First in human gene editing: a new era for IMD therapies
    2025/11/04
    Here’s a polished podcast blurb suitable for LinkedIn, BlueSky, or Apple Podcasts listings — written in the JIMD Podcast tone and style: ⸻ It’s one of the most talked-about breakthroughs of 2025, a first-in-human demonstration of in vivo gene editing to treat an inherited metabolic disease. In this episode, Kiran Musunuru and Rebecca Ahrens-Nicklas are joined by Julien Baruteau to unpack what this means for the field. They explore the science behind gene editing, the importance of ethical design, and the emotional weight of stopping therapy once enzyme function is restored. The conversation bridges the NEJM landmark paper (Musunuru et al., 2025) and the accompanying JIMD editorial (Rahman & Baruteau, 2025), reflecting on what this moment tells us about the future of metabolic medicine and how ready we are for it. First in Human Gene Editing for an Inherited Metabolic Disease Shamima Rahman, Julien Baruteau https://doi.org/10.1002/jimd.70056 Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease Kiran Musunuru, et al https://www.nejm.org/doi/10.1056/NEJMoa2504747
    続きを読む 一部表示
    48 分
  • Metabolic mysteries: A 61-year-old with rhabdomyolysis and lifelong episodic fatigue

    Metabolic mysteries: A 61-year-old with rhabdomyolysis and lifelong episodic fatigue
    2025/10/28
    Dr Samuel Mackenzie discusses the perplexing presentation of a 61-year-old man with rhabdomyolysis and a prolonged QT interval. Further exploration reveals a lifetime of episodic fatigue with illnesses. https://doi.org/10.1016/j.ymgmr.2025.101241
    続きを読む 一部表示
    8 分
  • IMD Research Round-Up: Untargeted metabolomics

    IMD Research Round-Up: Untargeted metabolomics
    2025/10/14
    With Rodrigo off caring for sick children, James Nurse joins Silvia Radenkovic to speak with Dr Judith Jans and Dr Devin Oglesbee about the emerging field of untargeted metabolomics. Authors’ opinions are their own and do not represent their institutions. Referenced papers include: Miller MJ, et al The emerging role of metabolomics analysis in genetic and genomic testing: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025 Jul 17:101493. doi: 10.1016/j.gim.2025.101493. Epub ahead of print. Evans AM, et al Dissemination and analysis of the quality assurance (QA) and quality control (QC) practices of LC-MS based untargeted metabolomics practitioners. Metabolomics. 2020 Oct 12;16(10):113. doi: 10.1007/s11306-020-01728-5. Wurth R, et al. An evaluation of untargeted metabolomics methods to characterize inborn errors of metabolism. Mol Genet Metab. 2024 Jan;141(1):108115. doi: 10.1016/j.ymgme.2023.108115. Epub 2023 Dec 15. Haijes HA, et al. Direct Infusion Based Metabolomics Identifies Metabolic Disease in Patients' Dried Blood Spots and Plasma. Metabolites. 2019 Jan 11;9(1):12. doi: 10.3390/metabo9010012. Willems AP, et al A one-year pilot study comparing direct-infusion high resolution mass spectrometry based untargeted metabolomics to targeted diagnostic screening for inherited metabolic diseases. Front Mol Biosci. 2023 Nov 2;10:1283083. doi: 10.3389/fmolb.2023.1283083. Haijes HA, et al. Aspartylglycosamine is a biomarker for NGLY1-CDDG, a congenital disorder of deglycosylation. Mol Genet Metab. 2019 Aug;127(4):368-372. doi: 10.1016/j.ymgme.2019.07.001. Epub 2019 Jul 9. PMID: 31311714. Hoegen B, et al Application of metabolite set enrichment analysis on untargeted metabolomics data prioritises relevant pathways and detects novel biomarkers for inherited metabolic disorders. J Inherit Metab Dis. 2022 Jul;45(4):682-695. doi: 10.1002/jimd.12522. Epub 2022 May 22. PMID: 35546254; PMCID: PMC9544878. Gao Q, et al A diagnostic algorithm for inherited metabolic disorders using untargeted metabolomics. Metabolomics. 2025 Jul 27;21(4):101. doi: 10.1007/s11306-025-02302-7. PMID: 40715884; PMCID: PMC12301266. Kerkhofs MHPM, et al. Cross-Omics: Integrating Genomics with Metabolomics in Clinical Diagnostics. Metabolites. 2020 May 18;10(5):206. doi: 10.3390/metabo10050206. Ashenden AJ, et al. The Multi-Omic Approach to Newborn Screening: Opportunities and Challenges. Int J Neonatal Screen. 2024 Jun 21;10(3):42. doi: 10.3390/ijns10030042. Liu N, et al. Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism. JAMA Netw Open. 2021 Jul 1;4(7):e2114155. doi: 10.1001/jamanetworkopen.2021.14155.
    続きを読む 一部表示
    43 分
  • Pharmacological chaperones in OTC deficiency

    Pharmacological chaperones in OTC deficiency
    2025/10/07
    Can small molecules stabilise OTC enzyme activity and change the outlook for urea cycle disorders? Dr Alexander Laemmle (University Hospital Bern) discusses pharmacological chaperones, a novel approach that strengthens enzyme stability in patient-derived liver models and offers new hope for female OTC carriers. Novel Treatment Strategy for Patients With Urea Cycle Disorders: Pharmacological Chaperones Enhance Enzyme Stability and Activity in Patient-Derived Liver Disease Models Adhuresa Ramosaj, et al https://doi.org/10.1002/jimd.70043 Induced pluripotent stem cell technology as diagnostic tool in patients with suspected ornithine transcarbamylase deficiency lacking genetic confirmation Adhuresa Ramosaj et al https://doi.org/10.1016/j.ymgmr.2023.101007
    続きを読む 一部表示
    19 分
  • Shortcast: Irish galactosemia outcomes

    Shortcast: Irish galactosemia outcomes
    2025/09/30
    Shortcast: Irish galactosemia outcomes by Journal of Inherited Metabolic Disease
    続きを読む 一部表示
    9 分
  • Penetrance, expressivity, and outcomes in classic galactosemia

    Penetrance, expressivity, and outcomes in classic galactosemia
    2025/09/23
    In this episode we discuss new insights into the variability of long-term outcomes in classic galactosemia. Joining me are Nikki Smith, Olivia Garrett, and Judy Fridovich-Keil, who together explore how complications in cognitive, motor, and speech domains emerge, cluster, and vary in severity across patients. Their study highlights both patterns and unanswered questions, illustrating the challenges families face and the importance of refining prognostic tools. Patterns of Penetrance and Expressivity of Long-Term Outcomes in Classic Galactosemia Nicole H. Smith et al. https://doi.org/10.1002/jimd.70020
    続きを読む 一部表示
    27 分
  • IMD Research Round-Up: Lysosomal Storage Disorders

    IMD Research Round-Up: Lysosomal Storage Disorders
    2025/09/16
    Silvia and Rodrigo are joined by Dr Ray Wang, Director of the multidisciplinary Foundation of Caring Lysosomal Storage Disorder Program at the Children's Hospital of Orange County. Silvia asks Dr Wang and Rodrigo (who also happens to be a researcher in this field) about cutting-edge advances in LSD research: from base editing in Pompe disease and patient-specific in vivo gene editing, to new biomarkers and scoring systems in Gaucher disease, insights into lipid dysregulation across lysosomal storage disorders, and the first clinical trial of anakinra in Sanfilippo syndrome. Papers discussed include: Christensen CL, et al Base editing rescues acid α-glucosidase function in infantile-onset Pompe disease patient-derived cells. Mol Ther Nucleic Acids. 2024 May 21;35(2):102220. doi: 10.1016/j.omtn.2024.102220. PMID: 38948331; PMCID: PMC11214518. Starosta RT, et al Predicting liver fibrosis in Gaucher disease: Investigation of contributors and development of a clinically applicable Gaucher liver fibrosis score. Mol Genet Metab. 2025 Feb;144(2):109010. doi: 10.1016/j.ymgme.2025.109010. Epub 2025 Jan 3. PMID: 39788861. Kell P, et al Secondary accumulation of lyso-platelet activating factors in lysosomal storage diseases. Mol Genet Metab. 2025 Jun 17;145(4):109180. doi: 10.1016/j.ymgme.2025.109180. Polgreen LE, et al Anakinra in Sanfilippo syndrome: a phase 1/2 trial. Nat Med. 2024 Sep;30(9):2473-2479. doi: 10.1038/s41591-024-03079-3. Epub 2024 Jun 21. Erratum in: Nat Med. 2024 Sep;30(9):2693. doi: 10.1038/s41591-024-03207-z. Musunuru K, et al Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease. N Engl J Med. 2025 Jun 12;392(22):2235-2243. doi: 10.1056/NEJMoa2504747.
    続きを読む 一部表示
    38 分
  • Adenosine Kinase

    Adenosine Kinase
    2025/09/09
    What if one enzyme could link metabolism, epigenetics, and therapy across conditions as diverse as epilepsy, cancer, and inflammation? In this episode, we dive into the fascinating world of adenosine kinase (ADK), an ancient enzyme that controls adenosine levels, energy balance, and even DNA methylation. Dr Detlev Boison join us to discuss their recent review in the Journal of Inherited Metabolic Disease, which reframes ADK not just as a metabolic regulator, but as a potential epigenetic drug target. From seizure suppression to cancer immunology, ADK sits at a crossroads, and could be a future key to metabolic and epigenetic medicine. Adenosine Kinase: An Epigenetic Modulator and Drug Target Uchenna Peter-Okaka, Detlev Boison https://doi.org/10.1002/jimd.70033
    続きを読む 一部表示
    24 分