NCT07448779

Investigating the Pathogenic Role of N-glycosylation in AL Amyloidosis: Molecular Bases, Diagnosis, and Treatment

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 100 (estimated)
• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Immunoglobulin light chain (AL) amyloidosis is caused by a typically small, minimally proliferating bone marrow plasma cell clone secreting a patient-unique, unstable, aggregation-prone, toxic light chain (LC). The amyloidogenicity of LCs is encrypted in their sequence, yet molecular determinants of LC pathogenicity remain obscure. N-glycosylation has been long suspected to be a determinant of LC amyloidogenicity based on anecdotal reports of individual AL patients with a clonal LC displaying this post-translational modification. It is hypothesized that N-glycosylation fundamentally contributes to determining the amyloidogenicity of immunoglobulin LCs in a subset of patients with AL and might influence its clinical phenotype. It is further proposed that the synthesis and secretion of unstable LCs that also have to be N-glycosylated might reverberate on the biology of the plasma cell clone, possibly modulating the sensitivity toward different drugs and might represent itself a therapeutic target. The objective of our study is now to elucidate the molecular role of LC N-glycosylation in AL amyloidosis, exploit it for risk assessment, and define its potential impact on the biology of the underlying plasma cell clone and its drug sensitivity.

Conditions

• AL Amyloidosis
• MGUS
• Multiple Myeloma
• Monoclonal Gammopathies

Timeline

• Start date: 2025-11-17
• Primary completion: 2027-05-30
• Completion: 2027-05-30
• First posted: 2026-03-04
• Last updated: 2026-03-04

Locations

1 site across 1 country: Italy