AAN 2023: TUDCA supplements lower inflammatory cell counts in progressive MS trial
But no significant clinical changes seen at 16 weeks of use in small Phase 1/2 study
Supplements with tauroursodeoxycholic acid (TUDCA) were generally well tolerated among people with progressive forms of multiple sclerosis (MS), according to findings from a small clinical trial.
Results also showed that patients given TUDCA supplements had lower levels of certain inflammatory immune cells than those given a placebo, but no differences in clinical outcomes were observed between the groups.
Further research is warranted to assess whether these supplements might be a treatment approach in MS, according to its researchers.
Kimystian Harrison, MD, with Johns Hopkins University School of Medicine, discussed trial findings at the American Academy of Neurology (AAN) 2023 Annual Meeting, being held in Boston and virtually on April 22-27.
Her presentation was titled, “Trial of Tauroursodeoxycholic Acid Supplementation in Patients with Progressive MS.” The work was funded by the National MS Society.
TUDCA, a bile acid, given as a daily supplement to PPMS and SPMS patients
TUDCA is a bile acid, a type of molecule naturally produced in the liver. Studies have suggested that bile acid activity is dysregulated in people with MS, and molecular receptors for bile acids have been found in disease lesions, suggesting they “could be a potential treatment target,” Harrison said.
In animal models of MS, TUDCA supplementation reduced disease-driving inflammatory activity.
To investigate the supplement’s effects in MS patients, scientists at Johns Hopkins conducted a Phase 1/2 clinical trial (NCT03423121).
Their study enrolled adults with progressive forms of MS, including primary progressive MS (PPMS) and secondary progressive MS (SPMS). These types of MS are marked by symptoms that gradually worsen over time independent of relapse activity, and have proven harder to treat than other MS types.
Participants were randomly assigned to take TUDCA (1 g twice daily; given as four 250 mg capsules) or a placebo for 16 weeks, about four months. The main objective was to assess the safety and tolerability of the supplements. Secondary measures included changes in bile acid levels, disability levels and quality of life, immune cells, and biomarkers of nerve cell damage.
A total of 54 patients, all white, were enrolled. Slightly more than half were female, and roughly half were using a disease-modifying therapy. Participants had been living with MS for at least six years, with some diagnosed more two decades earlier. At the start of the study, most participants required an aid to walk relatively short distances.
Safety data showed that patients given TUDCA supplements more commonly reported digestive side effects, such as nausea, vomiting, or diarrhea, compared with those given a placebo. One serious adverse event was reported in a patient given the TUDCA supplements, but Harrison did not provide details on the type of event, or whether it was considered related to TUDCA supplementation.
“Overall, [there was] no significant differences between the two groups in regards to serious adverse events,” she said.
Significantly lower levels of several inflammatory T-cells seen with treatment
Analyses of blood samples showed that TUDCA levels increased significantly for patients given the supplements, as expected. Levels of two other bile acids, called glycoursodeoxycholic acid and ursodeoxycholic acid, also increased significantly in patients given TUDCA supplements. None of the bile acids changed substantially over the study’s course for patients given a placebo.
Immune cell profiling showed that patients on TUDCA supplements experienced significant reductions in levels of several types of inflammatory T-cells compared with those given a placebo. These included subgroups of T-cells that produced the inflammatory molecules interleukin-1 (IL-1) and IL-17, as well as memory T-cell subgroups.
“TUDCA supplementation was safe, tolerable, and showed significant effects on bile acids and peripheral immune cells,” Harrison said.
Blood levels of neurofilament light chain (NfL), a marker of nerve damage, showed no apparent change with TUDCA supplementation compared with a placebo.
Levels of glial fibrillary acidic protein (GFAP) — a marker of damage to another type of neurological cell called astrocytes — tended to decrease over the course of the trial for patients given TUDCA, whereas they tended to increase among those on a placebo. However, the difference in GFAP levels was not statistically significant by the trial’s end, meaning it’s mathematically plausible that this difference could be due to random chance.
Analyses of clinical outcomes showed a statistically significant improvement in Multiple Sclerosis Functional Composite (MSFC) scores, a composite measure of walking function, dexterity, and cognition, among TUDCA group patients over the course of the trial. However, final MSFC scores did not significantly differ from those in the placebo group.
Similarly, other outcomes, including the Expanded Disability Status Scale (EDSS) and an MS-specific assessment of physical and mental life quality, did not show a statistically significant difference between the groups.
Harrison stressed that this was a small study running for about four months, limiting its ability to detect statistically meaningful associations. “The small sample size and short study period may not have been adequate to capture any significant effects on” measures of clinical efficacy, she said.
“Follow-up studies will help to determine whether this is a promising treatment strategy for progressive MS,” Harrison added.
Note: The Multiple Sclerosis News Today team is providing coverage of the American Academy of Neurology (AAN) 2023 Annual Meeting April 22-27. Go here to see the latest stories from the conference.