Investigational Drug Ibudilast Found to Be Neuroprotective in the Thalamus of Patients With Progressive MS

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In multiple sclerosis (MS), an errant immune response causes progressive brain and spinal cord demyelination, leading to cell death and tissue atrophy. The thalamus, a region of the brain responsible for processing sensory and motor information, is often affected in patients with MS.

Atrophy of the thalamus has been associated with several clinical outcomes of MS, including cognitive impairment, fatigue, pain, and mobility disorders. Because of this, thalamic atrophy is regarded as a highly important marker of MS disease progression.

Ibudilast is a small molecule being developed by biopharmaceutical company MediciNova for the potential treatment of MS. The company, based in La Jolla, California, is currently calling the oral formulation MN-166.

Ibudilast is a potential first-in-class glial attenuator designed to suppress the production of pro-inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha. In addition, it inhibits toll-like receptor 4 and macrophage migration inhibitory factor, both of which are elevated in the cerebrospinal fluid of individuals with MS and play a role in central nervous system inflammation.

The SPRINT-MS phase 2b study evaluated the effects of ibudilast in 255 participants with primary progressive MS (PPMS) and secondary progressive MS (SPMS). The study found a 48% decrease in brain atrophy in patients taking ibudilast versus those who received placebo and significant neuroprotective effects in the retina.

Kunio Nakamura, Ph.D., and his colleagues at the Cleveland Clinic in Cleveland, Ohio, analyzed data from the SPRINT-MS trial to determine whether treatment with ibudilast conferred similar neuroprotection in the thalamus among trial participants.

The new analysis results, published in the Multiple Sclerosis Journal earlier this month, showed that ibudilast exerted neuroprotection on intact tissue in the thalamus but did not significantly prevent thalamic atrophy over two years.

According to the researchers, the data suggests that “thalamic atrophy is more closely associated with global inflammatory activity than local tissue integrity”.

Ibudilast has been approved in Japan since 1989 to treat bronchial asthma and certain stroke complications. MediciNova is also investigating its use in other conditions, including amyotrophic lateral sclerosis and methamphetamine dependence. The company plans to launch a phase 3 trial to evaluate ibudilast’s effect on the rates of confirmed disability progression in patients with non-active SPMS.