Emerging and established biomarkers of oculopharyngeal muscular dystrophy

Ian C Smith; Shaoni Chakraborty; Pierre R Bourque; Marcos L Sampaio; Gerd Melkus; Hanns Lochmüller; John Woulfe; Robin J Parks; Bernard Brais; Jodi Warman-Chardon

doi:10.1016/j.nmd.2023.09.010

Emerging and established biomarkers of oculopharyngeal muscular dystrophy

Neuromuscul Disord. 2023 Nov;33(11):824-834. doi: 10.1016/j.nmd.2023.09.010. Epub 2023 Oct 6.

Authors

Affiliations

¹ The Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada.
² Faculty of Science, University of Ottawa, Ottawa, ON K1N 9B4, Canada.
³ Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Department of Medicine, The Ottawa Hospital/University of Ottawa, Ottawa, ON K1H 8L6, Canada; Eric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1Y 4E9, Canada.
⁴ Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Eric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1Y 4E9, Canada; Department of Medical Imaging, The Ottawa Hospital, Ottawa, Ontario K1Y 4E9, Canada; Department of Radiology, Radiation Oncology and Medical Physics, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
⁵ Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Eric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1Y 4E9, Canada; Department of Medical Imaging, The Ottawa Hospital, Ottawa, Ontario K1Y 4E9, Canada; Department of Physics, Carleton University, Ottawa, ON K1S 5B6, Canada.
⁶ The Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada; Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Department of Medicine, The Ottawa Hospital/University of Ottawa, Ottawa, ON K1H 8L6, Canada; Eric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1Y 4E9, Canada; Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada.
⁷ The Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada; Eric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1Y 4E9, Canada; Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON K1Y 4E9, Canada.
⁸ The Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada; Department of Medicine, The Ottawa Hospital/University of Ottawa, Ottawa, ON K1H 8L6, Canada; Eric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1Y 4E9, Canada.
⁹ Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec H3A 2B4, Canada.
¹⁰ The Ottawa Hospital Research Institute, Ottawa, ON K1Y 4E9, Canada; Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Department of Medicine, The Ottawa Hospital/University of Ottawa, Ottawa, ON K1H 8L6, Canada; Eric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1Y 4E9, Canada; Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada; Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec H3A 2B4, Canada. Electronic address: jwarman@toh.ca.

PMID: 37926637
DOI: 10.1016/j.nmd.2023.09.010

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is a rare, primarily autosomal dominant, late onset muscular dystrophy commonly presenting with ptosis, dysphagia, and subsequent weakness of proximal muscles. Although OPMD diagnosis can be confirmed with high confidence by genetic testing, the slow progression of OPMD poses a significant challenge to clinical monitoring and a barrier to assessing the efficacy of treatments during clinical trials. Accordingly, there is a pressing need for more sensitive measures of OPMD progression, particularly those which do not require a muscle biopsy. This review provides an overview of progress in OPMD biomarkers from clinical assessment, quantitative imaging, histological assessments, and genomics, as well as hypothesis-generating "omics" approaches. The ongoing search for biomarkers relevant to OPMD progression needs an integrative, longitudinal approach combining validated and experimental approaches which may include clinical, imaging, demographic, and biochemical assessment methods. A multi-omics approach to biochemical biomarker discovery could help provide context for differences found between individuals with varying levels of disease activity and provide insight into pathomechanisms and prognosis of OPMD.

Keywords: Biochemical; Biomarker discovery; Clinical; Imaging; Neuromuscular disorders; Pathology.

Publication types

Review

MeSH terms

Biomarkers
Blepharoptosis* / genetics
Deglutition Disorders*
Genetic Testing
Humans
Muscular Dystrophy, Oculopharyngeal* / genetics

Substances

Biomarkers