Development of peripheral nerve specific biomarker assays: from in vitro neuropathy models to clinical validation

Thesis

Clinical assessment of disease progression and effective design of clinical trials in peripheral neuropathy would benefit from objective biomarkers that closely reflect disease biology. This is particularly important in the inflammatory neuropathies, where reliable biomarkers of peripheral demyelination and axonal damage are needed to identify and measure active disease and responses to treatment.

This thesis describes the development of a novel ultrasensitive immunoassay to measure periaxin, a protein exclusively expressed in the peripheral nervous system, as a biomarker of peripheral demyelination. It also details the optimisation of a previously developed assay for peripherin, an intermediate filament predominantly expressed in peripheral axons, to serve as a biomarker of axonal injury. Together with neurofilament light chain (NfL), a validated biomarker of axonal damage, periaxin and peripherin form a complementary panel that improves diagnostic accuracy, disease monitoring, and supports biomarker-driven research in peripheral neuropathies. The work spans the full translational pathway, from biomarker conception and assay development to validation in patient samples, along with the use of cellbased models of neuropathy for biomarker validation. By combining clinical and in vitro work, this research establishes a biologically grounded framework for translating research findings into improved patient care.

Authors: Bellanti, R

• DOI: 10.5287/ora-m8vmg4okj
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: periaxin; biomarkers; peripheral neuropathy
• Subjects: Nerves, Peripheral--Diseases; Biochemical markers