Objective: To investigate the safety, tolerability, and capability of serum uric acid (UA) elevation of inosine 5′-monophosphate (IMP) in multiple system atrophy (MSA).
Background: Converging evidence has highlighted the neuroprotective effect of UA against the risk and progression of MSA. Strategies to increase serum UA levels were recognized to free from safety issues in previous clinical trials. No such clinical trials, however, to prove either safety or disease-modifying effect of increasing serum UA have been tried in MSA to date.
Method: The IMPROVE-MSA trial was a randomized, double-blind, placebo-controlled trial that consecutively recruited MSA patients from multiple sites located in South Korea. All the participants were assigned to placebo or IMP in a 1 to 1 ratio, and then followed up for 24 weeks. The primary endpoints included safety, tolerability, and alteration of the serum UA level during the follow-up period. The secondary endpoints were changes in neurological deficits measured by the UMSARS, MMSE, and MoCA using the linear mixed model.
Results: Finally, fifty-five participants were allocated to the active (n = 30) or the placebo group (n = 25), respectively. Serious adverse events did not occur more often in the active group (active vs placebo; 6 vs 4). Treatment was well tolerated in all study participants (study completion rate, active vs placebo; 22/30 (73.3%) vs 20/25 (80%); p = 0.56). Serum UA level (mean ± SD, mg/dL) was significantly increased from baseline (active vs placebo, 4.57 ± 0.93 vs 4.58 ± 1.07; p = 0.98) to study endpoint (6.96 ± 1.18 vs 4.43 ± 1.27; p < 0.001) in the active group than in the placebo group (time x group interaction; p < 0·001). The change in UMSARS scores did not differ between groups (time x group interaction; p = 0.86). However, the active group showed significantly better alterations in MoCA scores (p < 0.001) and a tendency for better alterations with marginal significance in MMSE scores (p = 0.09) than the placebo group.
Conclusion: Our data demonstrated that IMP treatment was generally safe and effectively raised serum UA levels in patients with MSA. The present data suggest that a further trial with a long-term follow-up is required to investigate whether UA elevating therapy will slow clinical progression in early MSA.
To cite this abstract in AMA style:
J.J Lee, J.H Yoon, S.J Kim, H.S Yoo, S.J Chung, Y.H Lee, S.Y Kang, H.W Shin, S.K Song, J.Y Hong, M.K Sunwoo, J.E Lee, J.S Baik, Y.H Sohn, P.H Lee. Inosine 5′-Monophosphate to Raise the Serum Uric Acid Level in Patients with Multiple System Atrophy (IMPROVE-MSA study): A Multi-center, Randomized, Double Blind, Placebo-controlled, Parallel Assigned Clinical Trial [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/inosine-5-monophosphate-to-raise-the-serum-uric-acid-level-in-patients-with-multiple-system-atrophy-improve-msa-study-a-multi-center-randomized-double-blind-placebo-controlled-parallel-assign/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/inosine-5-monophosphate-to-raise-the-serum-uric-acid-level-in-patients-with-multiple-system-atrophy-improve-msa-study-a-multi-center-randomized-double-blind-placebo-controlled-parallel-assign/