Analyzing Better Preclinical Models in Multiple Sclerosis Research: Christian Cordano, MD, PhD
The associate researcher at the University of California, San Francisco discussed a refined EAE model that could better replicate MS pathology, enabling deeper insights into demyelination, neuronal loss, and remyelination. [WATCH TIME: 6 minutes]
WATCH TIME: 6 minutes
“This model helped us understand that targeted autoreactive lymphocytes are able to induce disease, and more specifically, that targeting myelin with these lymphocytes allows us to obtain an EAE model that is more reproducible.”
Researchers recently developed a novel preclinical model using CAR-T technology to engineer human T-cells with a targeted immune response against myelin, potentially addressing a key limitation of traditional experimental autoimmune encephalomyelitis (EAE) models. Unlike EAE, which causes widespread demyelination, this model can produce discrete optic nerve (ON) lesions that closely resemble those seen in human MS. In a recent study, immunocompromised mice injected with myelin oligodendrocyte glycoprotein (MOG)-specific CAR-T cells exhibited CNS infiltration, optic neuritis-like damage, and axonal injury, as evidenced by increased serum neurofilament light chain levels and prolonged visual evoked potential (VEP) latency.
The study also revealed that these engineered T cells entered the retina through the ON head, which could mirror an unexplained feature of MS-related optic neuritis. Importantly, findings showed that treatment with clemastine, a remyelinating compound, significantly reduced lesion size in the ON, from 37% to 3.9%, and improved VEP latency. These findings suggest that this lesion-based model could enhance our understanding of T cell-mediated damage in MS and provide a valuable platform for testing remyelination therapies. By more accurately replicating human MS lesion pathology, the model could facilitate the development of treatments aimed at restoring ON function and mitigating disease progression.
The significance of this research was highlighted at the
REFERENCES
1. Cordano C, Simic M, Gupta S, et al. Modulating CNS Myelin Autoimmune Disease Using CAR T Cells. Presented at ACTRIMS Forum 2025; February 27 to March 1; West Palm Beach, Florida. CE1.1
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