Non-invasive Imaging Technique Reveals Ibudilast’s Neuroprotective Effect

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by Forest Ray PhD |

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eye movement and MS

A non-invasive retina imaging technique known as optical coherence tomography (OCT) provided evidence of the neuroprotective effect of ibudilast (MN-166) — an oral medication designed to reduce the body’s inflammatory responses —  in people with progressive forms of multiple sclerosis (MS).

The data also showed that OCT can be used to measure outcomes in progressive MS trials.

The results were published in the study “Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis,” in the Multiple Sclerosis Journal.

Thinning of the peripapillary retinal nerve fiber layer (pRNFL), one of the eye’s retina layers, is associated with the loss of brain volume and other measures of MS activity and progression. Thus, it has been proposed as a biomarker for MS progression, with OCT used as a way to measure it..

OCT uses light waves to take cross-sectional pictures of the eye’s retina, allowing researchers to measure the thickness of its various layers.

Ibudilast, developed by MediciNova, is thought to ease the neuroinflammation underlying MS symptoms by blocking the activity of four pro-inflammatory proteins — specifically IL-1 beta, TNF-alpha, IL-6, and TLR4 — while activating the anti-inflammatory signaling molecule IL-10.

In the SPRINT-MS trial (NCT01982942), researchers measured the changes in brain atrophy in response to either ibudilast treatment or a placebo over 96 weeks (about 22 months) among patients with primary or secondary progressive MS. OCT was used to track changes in the participants’ pRNFL in response to treatment.

Previous data from the trial showed a 48% reduction in brain volume loss with ibudilast treatment compared with the placebo group.

Now, the researchers analyzed in more detail the OCT data.

All of the participants in the SPRINT-MS trial underwent OCT every 24 weeks (about every six months) up to 96 weeks. Two different brands of OCT devices were used, depending on which was available at a given study site. This allowed the investigators to assess any equipment-specific effects.

In all, 183 participants were imaged with a Zeiss Cirrus SD-OCT and 61 with a Heidelberg Spectralis SD-OCT.

Regardless of the device used, pRNFL thickness increased overall in the ibudilast group (increase of 0.0424 micrometer per year) and decreased in the placebo group (decrease of 0.2630 micrometer per year).

Macular volume, that within the central area of the retina, decreased less among patients receiving ibudilast than those receiving a placebo, also regardless of the device. The decrease was 0.00503 mm3/year in the ibudilast group versus 0.03659 mm3/year in the placebo group, among those imaged by Spectralis. In the group imaged by Cirrus, the decrease was 0.00040 mm3/year among those give ibudilast versus 0.02083 mm3/year in the placebo group.

Additionally, the thickness of the ganglion cell inner plexiform layer, which contains synaptic connections between different kinds of nerve cells, decreased less in the ibudilast group (minus 0.4893 micrometer/year) than in the placebo group (minus 0.9587 micrometer/year).

Overall, the data suggested that ibudilast seems to reduce retinal thinning in progressive MS patients.

According to the team, this was the first multicenter clinical trial to employ OCT as an outcome in studying progressive MS.

“Together,” the researchers concluded, “these results potentially provide some support of a neuroprotective role for ibudilast in progressive MS and guide the use of OCT in future trials in progressive MS.”

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