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Abstract Details

Trial of Tauroursodeoxycholic Acid Supplementation in Patients with Progressive MS
S16 - MS Clinical Trials and Therapeutics
We have previously identified changes in the metabolome, specifically in bile acid (BA) metabolism in MS. We demonstrated that BA receptors are present in MS lesions, and TUDCA supplementation ameliorated disease in an animal model of MS and had direct anti-inflammatory effects on astrocytes and microglia. Trials in other neurodegenerative diseases have shown that TUDCA may be neuroprotective. The effects of TUDCA supplementation on MS are unknown but could provide a pathway for developing new therapies in PMS. 
The main aim of this trial was to assess safety and tolerability of tauroursodeoxycholic acid (TUDCA) supplementation in patients with progressive multiple sclerosis (pwPMS). Secondary objectives were to assess the effects on serum BA profile and clinical outcomes.
In this randomized, double-blinded trial, pwPMS were enrolled and randomized 1:1 to either receive TUDCA (1 g twice daily) or placebo for 16 weeks. Clinical visits occurred at 0, 8, and 16 weeks. Primary outcomes were safety and tolerability of TUDCA. Secondary outcomes included changes in BA serum levels and clinical outcomes. 
Of the 59 participants enrolled, 47 (80%) completed >2 visits and were included in the analysis (21 in placebo arm, 26 in TUDCA arm). The number of participants reporting adverse events was not significantly different between groups (10 in TUDCA arm vs 7 in placebo arm; p=0.72). The TUDCA group demonstrated significant increases over time in levels of TUDCA (p<0.001), glycoursodeoxycholic acid (p<0.001), ursodeoxycholic acid (p<0.001), and lithocholic acid (p=0.02). There was a significant improvement in MSFC (p=0.03), while no change was noted in EDSS and MSQOL-54 mental or physical composites in the TUDCA arm; no significant changes were noted in these outcomes in the placebo arm.
TUDCA supplementation was safe and tolerable in pwPMS, and led to significant increases in levels of several bioactive secondary BAs and improvement in MSFC score.
Authors/Disclosures
Kimystian Harrison, MD (Johns Hopkins University, School of Medicine)
PRESENTER
The institution of Dr. Harrison has received research support from National MS Society.
Peter A. Calabresi, MD, FAAN (Johns Hopkins University) Dr. Calabresi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Calabresi has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Disarm Therapeutics. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Investigation. The institution of Dr. Calabresi has received research support from Biogen. The institution of Dr. Calabresi has received research support from Annexon. Dr. Calabresi has received publishing royalties from a publication relating to health care. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Grant reveiwer with Myelin Repair Foundation. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker for CME with NYAS. Dr. Calabresi has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Academic CME. Dr. Calabresi has a non-compensated relationship as a Consultant with Apellis that is relevant to AAN interests or activities.
Pavan Bhargava, MD, FAAN (Johns Hopkins University) The institution of Dr. Bhargava has received research support from EMD Serono. The institution of Dr. Bhargava has received research support from Amylyx pharmaceuticals. The institution of Dr. Bhargava has received research support from Genentech. The institution of Dr. Bhargava has received research support from GSK.
Elias S. Sotirchos, MD (Johns Hopkins University) Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ad Scientiam. Dr. Sotirchos has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viela Bio. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Sotirchos has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Sotirchos has received research support from National Institutes of Health. The institution of Dr. Sotirchos has received research support from National Multiple Sclerosis Society. The institution of Dr. Sotirchos has received research support from Sumaira Foundation. The institution of Dr. Sotirchos has received research support from Genentech. Dr. Sotirchos has received personal compensation in the range of $500-$4,999 for serving as a Ad Hoc Reviewer with National Institutes of Health.
Soonmyung Hwang Mr. Hwang has nothing to disclose.
Dimitrios Christos Ladakis, MD (Johns Hopkins University, School of Medicine) Dr. Ladakis has nothing to disclose.