Ibudilast was shown to have a neuroprotective effect in the MS-SPRINT trial undertaken years ago and there was some benefit noted but the question we have to pose is, where is ibudilast… I think I can answer this and this is in the maggot pile… But it raises a serious question we have posed many times, where next?
This was a study supported by a company but paid for by the NIH/MS Society… There no plan to get this to people with MS. I guess there is no patent and also how does it work to get a similar chemical to develop?
It is a PDE4 inhibitor, they have not done well in MS and they have a side effect profile, such as a nausea.
However it begs the question without a plan to actually get an agent to people in need… it is a lot of money spent to go nowhere. We have asked what is the plan, should a charity supported trial be positive. If it is a phase II (surrogate e.g. imaging outcome), then you need a phase III clinical outcome but then what will the regulators approve it and who will be responsible for the monitoring? It is imperative the path is clear before you start. We asked about STAT2 and we don’t need to worry as it wasn’t positive but it was never clear what the plan next is. Octopus is a trial what is the path to get to people when an positive trial is performed it is an important question to answer
Ramezani A, Varshosaz J, Darash S, Ebne-Ali-Heydari Y. A comprehensive systematic review of Ibudilast as a neuroprotective therapy for progressive multiple sclerosis. Mult Scler Relat Disord. 2025 Oct 19;104:106807.
Background: Ibudilast, a phosphodiesterase inhibitor, has shown promise potential in Multiple sclerosis (MS) therapy.
Objectives: This systematic review synthesizes evidence from clinical trials to assess the neuroprotective effects of ibudilast in progressive MS, focusing on brain atrophy, disability progression, and safety outcomes.
Methods: Following PRISMA 2020 guidelines, a systematic search of PubMed, Embase, Web of Science, and Scopus (1995-2025) for randomized controlled trials and prospective studies was conducted. Thirteen studies met inclusion criteria, including the phase 2 SPRINT-MS trial (n = 255). Outcomes included neuroimaging metrics (brain atrophy, lesion activity), disability progression (Expanded Disability Status Scale [EDSS]), and safety. Risk of bias was assessed using Cochrane RoB 2.0 and ROBINS-I tools.
Results: Ibudilast significantly slowed whole-brain atrophy by 48 % versus placebo (p = 0.04), with pronounced effects in primary progressive MS (PPMS; p < 0.01). Gray matter atrophy was reduced by 35 % (p = 0.038), and thalamic integrity was preserved (p = 0.03). Retinal neurodegeneration was attenuated in PPMS (79 % reduction, p = 0.003). Chronic active lesion volume decreased by 23 % (p = 0.003), suggesting suppression of compartmentalized inflammation. No significant impact on EDSS progression or serum neurofilament light chain levels was observed.
Conclusions: Ibudilast demonstrates robust neuroprotection in progressive MS, particularly PPMS, with benefits on brain and retinal atrophy and chronic lesion activity.
Source: multiple-sclerosis-research.org