Ibudilast is a small molecule drug that has shown promise in slowing brain atrophy rates in progressive multiple sclerosis (MS), a form of MS characterized by gradual worsening of neurological function and brain tissue loss. It works primarily by inhibiting enzymes called phosphodiesterase type-4 (PDE4) and reducing inflammatory cytokines, including macrophage migration inhibitory factor (MIF). These actions help modulate the immune response and reduce neuroinflammation, which are key contributors to brain tissue damage and atrophy in progressive MS.
Brain atrophy in progressive MS reflects the loss of neurons and their connections, leading to shrinking of brain regions and worsening disability. Ibudilast’s ability to inhibit PDE4 and inflammatory molecules helps protect brain cells from ongoing damage and may slow the rate at which brain tissue deteriorates. This neuroprotective effect is important because progressive MS typically shows less inflammation visible on standard MRI scans but more diffuse neurodegeneration, which is harder to treat.
Clinical trials, such as the SPRINT-MS study, have investigated ibudilast’s effects on brain atrophy using advanced imaging techniques like diffusion tensor imaging (DTI). DTI measures the integrity of white matter tracts by assessing how water molecules diffuse along nerve fibers. In the SPRINT-MS trial, patients with secondary and primary progressive MS treated with ibudilast showed significantly less deterioration in specific brain regions, including the cingulum and cerebellar peduncles, compared to placebo. These areas are important for cognitive and motor functions. The treated group’s radial diffusivity—a marker of tissue damage—remained stable or improved, indicating preservation of brain tissue, whereas the placebo group showed worsening diffusivity consistent with ongoing tissue loss.
The protective effect of ibudilast on brain atrophy is thought to arise from its multiple mechanisms: reducing harmful inflammation, inhibiting enzymes that break down cellular signaling molecules, and possibly promoting repair processes in the nervous system. By dampening chronic inflammation and protecting nerve cells, ibudilast may slow the progression of disability in patients with progressive MS.
Ibudilast is currently in late-stage clinical development for progressive MS and other neurodegenerative diseases. Its safety profile appears favorable, and ongoing studies aim to confirm its long-term benefits on brain atrophy rates and clinical outcomes. If successful, ibudilast could represent one of the first therapies to specifically target neurodegeneration and brain tissue loss in progressive MS, addressing a critical unmet need in this patient population.
In summary, ibudilast affects brain atrophy rates in progressive MS by inhibiting inflammatory pathways and enzymes that contribute to neurodegeneration, thereby preserving brain tissue integrity as shown by advanced imaging studies. This neuroprotective action offers hope for slowing disease progression and improving quality of life for people living with progressive MS.
