Uric Acid Correlated with Disease Activity in Multiple Sclerosis

A metaanalysis shows that levels of an antioxidative endogenous metabolic byproduct—uric acid—are correlated with disease activity in multiple sclerosis.

In a study published in the journal Clinical Chemistry and Laboratory Medicine on September 20, 2014, investigators Moccia et al identified uric acid as a potential biomarker in the progression of multiple sclerosis (MS) disability.¹

Uric acid, which has activity as a natural scavenger of oxygen radicals, is present in the bloodstream as a breakdown product of purines (adenine and guanine). In previous animal studies, uric acid has been shown to have some potential as a treatment for MS.¹

Results of these studies led investigators in the present study to search for a relationship between MS severity and levels of uric acid. In the case-control study using propensity score matching, investigators paired 362 patients with MS to 181 control individuals without MS.¹

To reduce variation between populations, investigators corrected data for patient age, gender, and kidney function. Upon regression analysis, investigators identified a significant association between low levels of serum uric acid among patients with MS compared with controls, with an R-squared value of 30.4% and statistical significance for the correlation (P = .014).¹

Lower levels of uric acid were associated with a longer disease duration, a longer duration since diagnosis, and higher Expanded Disability Status Scale (EDSS) scores (P <.001, all comparisons). These findings suggest that uric acid may be a biomarker of MS disability and progression, although past studies reveal that uric acid may have a limited role as a marker of treatment response or as a therapeutic target in MS.¹

For instance, a 2006 analysis published in the journal Clinical Neurology and Neurosurgery, found that uric acid levels did not change as a result of immunomodulatory or immunosuppressive drug treatment among patients with MS.²

Additionally, in the Association of Inosine and Interferon beta in relapsing-remitting Multiple Sclerosis (ASIIMS) trial, investigators administered a precursor of uric acid—inosine&mdash;to patients with MS in conjunction with interferon-beta over the course of 2 years. The results of this trial were negative and uric acid did not have any additional benefit on disability outcomes versus interferon-beta alone.³

In spite of the negative result of the ASIIMS trial, antioxidative drugs may still have a future in treatment of multiple sclerosis. However, uric acid may be a biomarker—not a treatment modality. Studying uric acid may help physicians predict the progression of multiple sclerosis in patients, although previous research shows that uric acid levels do not predict response to treatment² and supplementation with uric acid does not alter the progression of disability in MS.³

Further study will be necessary to determine whether or not drugs that mimic the effects of uric acid are of any therapeutic value in patients with MS.

References:

• Moccia M, Lanzillo R, Palladino R, et al. Uric acid: a potential biomarker of multiple sclerosis and of its disability. Clin Chem Lab Med. 2014.
• Rentzos M, Nikolaou C, Anagnostouli M, et al. Serum uric acid and multiple sclerosis. Clin Neurol Neurosurg. 2006;108(6):527-531.
• Gonsette RE, Sindic C, D'hooghe MB, et al. Boosting endogenous neuroprotection in multiple sclerosis: the ASsociation of Inosine and Interferon beta in relapsing- remitting Multiple Sclerosis (ASIIMS) trial.Mult Scler. 2010;16(4):455-462.