Ibudilast treatment found to protect tissue integrity in brain in MS

Treatment with ibudilast — an anti-inflammatory being developed to treat people with progressive forms of multiple sclerosis (MS) — significantly preserved tissue integrity in a brain region called the thalamus in patients in a clinical trial, according to new analyses from SPRINT-MS.

While the therapy appeared to exert these neuroprotective effects on tissue that remained, researchers noted that it did not significantly prevent the loss, or atrophy, of thalamic tissue over a period of two years.

The study, “Effect of ibudilast on thalamic magnetization transfer ratio and volume in progressive multiple sclerosis,” was published in the Multiple Sclerosis Journal.

Recommended Reading

June 24, 2021 News by Somi Igbene, PhD

MIND Diet May Protect Brain Tissue in MS

Researchers aim to determine effects of ibudilast in brain’s thalamus

In MS, autoimmune attacks lead to the progressive loss of myelin, the fatty substance that surrounds nerve cells, protecting them and facilitating cell-to-cell communication. This loss of cellular health and integrity over time leads to cell death, and tissue atrophy, or shrinkage, is observed throughout the brain.

One affected region is the thalamus, which serves as the brain’s main relay station for processing sensory information. Data indicate that there is early thalamic damage in MS brain tissue.

Given that thalamic atrophy also has been associated with clinical measures — including disability progression, cognitive impairment, and fatigue — in MS, it is thought to be a highly relevant disease marker.

Ibudilast is a molecule designed to reduce the levels of pro-inflammatory signaling molecules that contribute to inflammation and nerve cell damage in MS. An oral formulation called MN-166 is being developed by MediciNova as potential MS treatment.

A Phase 2b U.S. study, called SPRINT-MS (NCT01982942), investigated the effects of ibudilast in 255 people with primary progressive (PPMS) and secondary progressive MS (SPMS), with or without relapses.

Participants were randomly assigned to receive oral ibudilast or a placebo for 96 weeks, or nearly two years. Patients could continue treatment with glatiramer acetate (sold as Copaxone or generics) or interferon-beta therapies during the trial.

The study found that ibudilast significantly slowed the rate of brain atrophy, by 48%, and exerted neuroprotective effects in the retina, the light-sensitive layer of the eye.

In the new analysis, the scientists investigated whether the treatment among SPRINT-MS participants had shown similar neuroprotective effects in the thalamus.

An advanced MRI technique called magnetization transfer ratio (MTR) was used to estimate tissue integrity in the thalamus. This measure often is used to test for the loss of myelin, with an MTR reduction indicating myelin loss, known as demyelination.

Recommended Reading

March 3, 2023 News by Marisa Wexler, MS

ACTRIMS 2023: Ibudilast did not lift life quality in progressive MS trial

Ibudilast not found to prevent loss of brain tissue

The results showed that ibudilast was associated with significantly preserved tissue integrity in the thalamus compared with the placebo. Specifically, the average MTR in the ibudilast group increased by 0.08% per year, whereas it decreased by 0.09% annually in the placebo group.

A patient’s overall disability, as assessed by the Expanded Disability Status Scale (EDSS), had a small, but significant effect on thalamic MTR changes. Particularly, MTR declined annually by an average of 0.13% for people who exhibited disability progression (and had an increase in EDSS scores) during the trial, whereas it increased by 0.04% for those who did not progress.

No significant differences in overall thalamic atrophy — the change in tissue volume over time — were observed between the two groups. Moreover, there were no statistically significant differences between PPMS and SPMS patients in terms of treatment effects in the thalamus.

In previous trial analyses, it was found that ibudilast significantly slowed MTR in normal-appearing brain tissue but did not affect the formation of new or enlarging brain lesions.

Together, the findings suggest that while ibudilast has neuroprotective, and potentially regenerative properties, it is not actively combating the inflammation that causes lesions to form, and might not prevent thalamic volume loss as robustly as other therapies that significantly affect lesion development., according to the team.

“Our data suggest that thalamic atrophy may be less responsive to neuroprotective agents that lack anti-inflammatory actions,” the team noted.

Nonetheless, “these findings suggest that thalamic MTR is clinically relevant and may be useful in phase II trials of neuroprotective strategies, as an outcome to predict clinical effect of progression,” the team concluded.