The role of brain ATP abnormalities in MS disease progression

A 3-year prospective observational study investigating ATP changes in MS via T7 MRSI, comparing patients with and without vascular disease risk factors (VDRF), demonstrated that VDRF-positive patients had lower brain ATP rates and total brain parenchymal volumes than VDRF-negative patients at baseline. Dr Vijayshree Yadav (Oregon Health & Science University, USA) presented the preliminary results of the study and explained the link between ATP depletion, VDRF, and accelerated disease progression in MS [1].

VDRF are common in MS, affecting over 50% of the patients, with hyperlipidaemia, hypertension, and obesity being the most prevalent [2]. Disease progression in MS is increased by presence of VDRF, but the mechanisms behind this association are not well known. It has been hypothesised that VDRF leads to a reduced substrate delivery, which causes impaired mitochondrial function. Subsequently, this could lead to increased high-energy phosphate metabolite deficiencies, increased neurodegeneration, and disease progression.

In the presented study, baseline VDRF-positive (n=29, mean age 56.3) and VDRF-negative (n=23, mean age 52.4) MS patients were subjected to 7T MRSI to assess differences in high-energy phosphate metabolites, brain volumes, and associated disease progression. Preliminary results of the MRSI analysis showed that VDRF-positive patients had approximately 5% lower brain ATP rates than VDRF-negative patients. The MRI signal changes were consistent over white and grey matter. Moreover, the VDRF-positive group had lower total brain parenchymal volumes (1,017) than the VDRF-negative group (1,099), representing an 8% difference. Patients in the VDRF-positive group had higher neurological disability, indicated by EDSS scores.

Dr Yadav argued that ATP reductions in VDRF-positive MS patients are possibly caused by lower cranial blood flow and are related to mitochondrial dysfunction, which contributes to an accelerated disease progression.

1. Yadav V, et al. Vascular Disease Risk Factors in Multiple Sclerosis (MS) is Associated with Brain Adenosine Triphosphate Abnormalities: Dysmetabolism May Drive MS Disease Progression. S2.004, AAN 2021 Virtual Congress, 17-22 April.
2. Marrie R, et al. Neurology. 2010 Mar 30;74(13):1041-7.

Posted on 22 April 202117 June 2021