Enhancing global collaboration for earlier detection and prevention of MS

Researchers and other experts, including people affected by MS, gathered in a virtual workshop in 2021. The aim was to understand the earliest stage when MS begins (the ‘prodromal phase’), and to identify key research priorities that will enhance early detection of MS, with the ultimate goal of preventing onset of MS disease symptoms.

The MS Society of Canada, in partnership with the National MS Society (USA), convened the virtual workshop. The meeting was led by Canadian researchers, Dr Helen Tremlett and Dr Ruth Ann Marrie, and attended by MS organisations including MSIF. A prodrome is an early set of signs or symptoms indicating the onset of a disease (read more here and FAQ below). The workshop aimed to identify key research priorities to further our knowledge of the MS prodrome, enhance global collaboration, and accelerate progress. Participants included international researchers and clinicians with expertise in MS, neurology, epidemiology, genetics, imaging and immunology, and people affected by MS. In addition, researchers with expertise in type 1 diabetes and Parkinson’s disease attended to share learnings from diseases that already have defined prodromal phases. The outcomes of this workshop are reported in a recent article published in Nature Reviews Neurology, as well as in this personal view from Sharon Roman in the Multiple Sclerosis Journal.

The workshop identified the following key research priorities needed to develop criteria for identifying individuals within the prodromal stage who are at greatest risk of being diagnosed with MS:

• Obtain worldwide prevalence estimates for MS that include age and biological sex. Gather global population-based data on people with MS that includes information on their age and biological sex. This information will be used, together with other measures, to calculate the probability that an individual will develop MS.
• Identify new markers of the prodromal stage of MS. Additional markers are needed to better identify those at greatest risk of MS within the prodromal period. Markers also need to be identified and validated in populations with differing ancestries. The markers can be clinical, genetic, imaging, or blood or spinal fluid-based.
• Quantify the association between prodromal markers and the probability or risk of developing MS. Once markers have been identified, they need to be assessed for the extent to which they indicate someone might develop MS.
• Develop and validate criteria for the prodromal stage of MS for research. Use identified markers to develop prodromal criteria that can be used to assess an individual’s likelihood of developing MS over a defined period. These criteria can be used by researchers to identify those at greatest risk of MS and enrol them in clinical trials that are testing interventions aiming to prevent the onset of MS symptoms.

These criteria will help guide the design of effective research studies focusing on the MS prodrome. There is still more work to be done, but with support from people with MS, patient organisations, industry, regulators, researchers and MS clinicians, we are making progress. Having globally agreed criteria for studying the MS prodrome will help us better recognise the earliest stages of MS, diagnose it swiftly, and develop treatments that can delay the onset of symptoms.

Frequently Asked Questions about the MS prodrome:

What is a prodrome?

A prodrome is an early, often non-specific, set of signs or symptoms indicating the onset of a disease, before more typical symptoms or signs appear.

Do other diseases have prodromal stages?

Yes, prodromal stages are well-recognized in several neurodegenerative and immune-mediated diseases such as Parkinson’s disease, schizophrenia, type 1 diabetes and rheumatoid arthritis.

Does MS have a prodromal stage?

MS is an inflammatory and neurodegenerative disease in which both genetic and environmental factors contribute to disease development. This is emerging evidence to support the presence of a prodromal stage in MS.

Research has shown increased hospitalisations, physician visits and prescription drug use is increased at least five years before MS symptom onset or a first demyelinating event. Common non-specific symptoms such as headache and other pain-related disorders, fatigue, urinary symptoms, and psychiatric symptoms have been identified in this period before MS symptom onset, a first demyelinating event, or MS diagnosis. Additionally, blood levels of a biomarker, neurofilament light chain (NfL) that detects neurodegeneration, has been shown to be elevated 6 years before MS signs or symptoms were reported.

How will a better understanding of the MS prodromal stage benefit those living with MS?

If we can better identify individuals in a prodromal stage of MS, it may offer the opportunity to prevent, or delay development of classical symptoms of MS. To get here, we need to fully characterise and understand the MS prodrome and have a validated set of criteria to ascertain individual’s risk, in addition to understanding windows of opportunity for intervention to prevent and delay onset of MS.

With thanks to the MS Society of Canada for authoring the original version of this article here.