Biomarkers of multiple sclerosis disease progression and treatment response

Effective treatment for progression of disability in multiple sclerosis (MS) remains an urgent unmet need. Developing an effective approach to treating progression is complex, as people with MS respond differently to different therapies. Also, progression in early MS is subtle yet contributes to long-term disability. Progression may be driven by inflammation and nerve degeneration, which are different disease mechanisms that may require different treatment methods.

To treat progression, it is essential to have accurate markers for it. However conventional measures of disease activity, such as relapses, disability and brain imaging, may not detect subtle progression and they do not identify the underlying drivers of progression.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are components of damaged nerve fibres and supporting brain cells, respectively. They are sometimes seen at higher levels in the blood in people with neurological diseases. They reflect nerve degeneration and brain inflammation, respectively, and hold promise for monitoring disease and guiding treatment.

In this project, Dr Winston Dzau will be investigating whether:

• Conventional markers of disease activity can be used to identify people with progressive disease who may be more likely to respond to particular treatments.
• NfL can be used to predict response to treatment in progressive disease.
• NfL and GFAP can be used to predict disease progression, even in people who seem otherwise stable; and
• Whether NfL and GFAP can be used to measure how much inflammation nerve degeneration each contribute to driving disease progression.

Dr Dzau and his team expect this project will help support personalised treatment decisions, using these blood markers that can identify subtle signs of disease progression. The project will help refine the classification of MS based on individual drivers of progression. This will be an important step towards effectively treating the underlying mechanisms of disease progression.