Abstract: INFO12-FR
Progress and Promise: N-Acetylmannosamine (ManNAc) as a Therapy for Glomerular Diseases
Session Information
- Informational Posters - 2
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Ganguli, Anirban, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Bolanos, Jonathan Alexis, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Malicdan, May christine, National Human Genome Research Institute Medical Genetics Branch, Bethesda, Maryland, United States
- Ashton, Andrea, National Human Genome Research Institute, Bethesda, Maryland, United States
- Wilkins, Kenneth J., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Kopp, Jeffrey B., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
- Gahl, William, National Human Genome Research Institute Undiagnosed Diseases Program, Bethesda, Maryland, United States
- Huizing, Marjan, National Human Genome Research Institute Medical Genetics Branch, Bethesda, Maryland, United States
Description
Background: Terminal sialic acid residues give anionic charges to proteins and lipids which contribute to the charge-dependent glomerular filtration barrier. We previously reported that glomerular hyposialylation is common in a variety of glomerular diseases, underscoring a novel pathway associated with podocyte dysfunction. In nephrotic mouse models, oral ManNAc, a sialic acid precursor, restored glomerular sialylation and significantly reduced proteinuria. ManNAc is, currently, being studied for therapy of a rare genetic disease, GNE myopathy (NCT04231266).
Phase-1 Study (NCT02639260) Results: Oral ManNAc, when given to 7 nephrotic patients with primary glomerular disease, was found to be safe and well-tolerated.
Phase-2 Study Design: An open-label phase 2 study is now planned to probe the long-term safety, and efficacy of ManNAc in 15 adults with biopsy-proven focal segmental glomerulosclerosis (FSGS) with UPCR >2g/g, eGFR >45 ml/min/1.73m2 and glomerular hyposialylation. Participants will receive oral ManNAc 2g twice daily for 12 weeks. Primary outcomes will be % reduction in UPCR, drug safety and tolerability. Secondary outcomes will include long-term pharmacokinetics and % of patients with partial and complete remission while exploratory outcomes will measure the impact of therapy on Patient-Reported Outcomes (PROs) and eGFR slope. The study is currently undergoing completion of review at the Institutional Review Board and is anticipated to start enrolling patients by December 2024.
Conclusion: ManNAc appears to be a safe, well-tolerated, and easily administered therapy with the potential to reduce proteinuria in primary glomerular disease. The upcoming phase 2 trial will further ascertain the safety and efficacy of ManNAc. If successful, the trial could usher in an era of precision-based therapy in both primary and secondary glomerular diseases associated with defective glomerular sialylation.
Funding
- National Institutes of Health