Anti–myelin-associated glycoprotein neuropathy: Where do we stand?

Amro Maher Stino, Bakri Elsheikh, Jeffrey A. Allen

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Myelin-associated glycoprotein (MAG) is a transmembrane glycoprotein concentrated in periaxonal Schwann cell and oligodendroglial membranes of myelin sheaths that serves as an antigen for immunoglobulin M (IgM) monoclonal antibodies. Individuals who harbor anti-MAG antibodies classically develop a progressive autoimmune peripheral neuropathy characterized clinically by ataxia, distal sensory loss, and gait instability, and electrophysiologically by distally accentuated conduction velocity slowing. Although off-label immunotherapy is common, there are currently no proven effective disease-modifying therapeutics, and most patients experience slow accumulation of disability over years and decades. The typically slowly progressive nature of this neuropathy presents unique challenges when trying to find effective anti-MAG therapeutic agents. Drug development has also been hampered by the lack of validated outcome measures that can detect clinically meaningful changes in a reasonable amount of time as well as by the lack of disease activity biomarkers. In this invited review, we provide an update on the state of clinicometric outcome measures and disease activity biomarkers in anti-MAG neuropathy. We highlight the insensitivity of widely used existing clinicometric outcome measures such as the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score as well as the INCAT sensory subscore in anti-MAG neuropathy, referencing the two previous negative randomized controlled clinical trials evaluating rituximab. We then discuss newly emerging candidate therapeutic agents, including tyrosine kinase inhibitors and enhanced B-cell–depleting agents, among others. We conclude with a practical approach to the evaluation and management of anti-MAG neuropathy patients.

Original languageEnglish (US)
Pages (from-to)823-832
Number of pages10
JournalMuscle and Nerve
Volume68
Issue number6
DOIs
StatePublished - Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.

Keywords

  • anti-MAG neuropathy
  • biomarker
  • immunotherapy
  • outcome measure
  • rituximab

PubMed: MeSH publication types

  • Journal Article
  • Review

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