Glycosylation, CDGs & Role of Sugars Beyond Energy Production | Eva Morava | 207

Short Summary: The science of glycosylation, its impact on health, and potential treatments for congenital disorders of glycosylation (CDGs).

About the guest: Dr. Eva Morava is a pediatric geneticist originally from Hungary, who has specialized in inborn errors of metabolism, particularly CDGs. She has a background in pediatrics and genetics from training in Hungary and the U.S., and currently leads the genetics and genomics department at Mount Sinai.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and to everyone on YouTube. Partial versions are available elsewhere.

Episode Summary: Dr. Eva Morava discusses the critical role of glycosylation in biology, where sugars are not just used for energy but in modifying proteins to perform their functions. She explains how defects in this process lead to CDGs, a group of rare genetic disorders. The conversation covers the mechanics of glycosylation, clinical presentations of CDGs, current research on treatments including dietary interventions and gene therapy, and the broader implications of glycosylation in health, such as in liver disease and cancer.

Key Takeaways:

Glycosylation Basics: Sugars are attached to proteins (glycosylation) to modify their structure and function, influencing everything from clotting to immune response.

CDGs: These disorders are caused by genetic defects in the glycosylation process, leading to a wide array of symptoms because many proteins require glycosylation to function correctly.

Clinical Variability: CDGs can range from severe, multi-systemic presentations to relatively mild cases, affecting life expectancy and quality of life variably.

Therapeutic Approaches: Current research includes drug repurposing for enzyme activity enhancement, dietary interventions with special sugars like mannose, and gene therapy, with some trials underway.

Liver Connection: A significant portion of glycosylation occurs in the liver; thus, liver diseases like non-alcoholic fatty liver disease can impact glycosylation.

*Not medical advice.

00:02:52 Eva Morava Intro
00:06:24 Glycosylation Mechanics
00:12:35 Dietary Impact on Glycosylation
00:17:04 Clinical Manifestations of CDG
00:22:34 Sugars & Their Role in Glycosylation
00:29:21 Frequency & Challenges of CDG
00:35:29 Current Therapeutic Research in CDG
00:41:27 Glycosylation in Common Health Issues
00:45:09 Future of CDG Research with Organoids