Multiple sclerosis (MS) is the most common medical cause of neurological disability in young adults, afflicting more than 120,000 people nationally, and it is increasing in prevalence.
In most people with MS the disease starts with a relapsing remitting course where discrete episodes of inflammatory demyelination within the brain and spinal cord (relapses) are interspersed with longer periods of relative recovery and stability (remission). These areas of inflammation show as discrete lesions on magnetic resonance imaging (MRI). These MRI lesions can be used as biomarkers for clinical trials which have led to an increasing array of disease modifying treatments for this phase of the disease. These disease modifying therapies all work by reducing neuro inflammation.
However after a lag for 10-15 years most people will develop progressive MS caused by actual nerve cell death (neurodegeneration), where functional abilities like walking, balance, vision, pain, bladder and bowel function cumulatively and irreversibly worsen over time. Progressive MS is responsible for the majority of healthcare expenditure and morbidity of MS but critically unlike the earlier relapsing remitting stage of the disease there are no available treatments; anti-inflammatory treatments that are effective in the relapsing remitting phase of the disease have no effect. Research to understand and prevent the accumulation of disability in progressive MS has been identified by the MS Society UK, the James Lind alliance, and the International Progressive MS alliance as the number one priority for research funding in MS.
Experimental and pathological studies show that mitochondrial dysfunction may lead to progressive neurodegeneration. This is an important observation as it indicates a target for the development of future disease modifying treatments for progressive MS, however it is not understood to what extent this occurs in vivo, and whether this would be amenable to treatment.
Phosphorous MR (31-P) is a promising technique to explore these pathologically derived hypotheses in vivo. Phosphorous MR spectroscopy is able to quantify high and low energy phosphorous metabolites, and by measuring the ratio between the two it is possible to quantify mitochondrial energy production with respect to demand.
The aim of the funding would be to obtain pilot data on the use of phosphorous MR spectroscopy in patients with progressive MS alongside other more conventional MRI measures of MS pathology (structural MRI and proton spectroscopy). The objective of the project is to assess whether significant alterations in energy metabolic substrates are seen in patients with progressive MS as compared to healthy controls in order to plan future longitudinal studies. Our hypothesis is that phosphorous spectroscopy will be sensitive to the pathology underlying clinical progression in MS, could further our understanding of the disease, help clinicians with diagnosis, and serve as a biomarker to help select and monitor patients during trials of potential disease modifying therapies for this currently untreatable condition.