A University researcher told the RDAC that new preclinical work implicates cytotoxic CD8 T cells in the neuropathology of Krabbe disease and that therapies which block T-cell trafficking produced marked benefit in animal models.

The nut graf: Steven Crocker said his lab found abundant CD8 T cells in affected white-matter areas in mouse, dog and human tissue and that depleting or blocking these cells preserved myelin and axons and substantially improved survival in mouse models, suggesting that repurposing existing immunomodulatory drugs could offer a path toward modifying disease course.

Crocker summarized experiments in which anti-CD8 approaches and natalizumab-like antibodies (which block T-cell trafficking) reduced pathology and markedly extended survival in the twitcher mouse model. "We were able to show in the graphs...100 percent of the mice that were treated with the CD8 treatment...survived," he said, describing preserved myelin and axons in treated animals compared with untreated littermates.

He said Krabbe disease is rare (roughly 1 in 100,000 in many populations), noted newborn-screening improvements that allow earlier diagnosis in some places, and said repurposing approved immunotherapies could expand therapeutic windows and provide neuroprotection that complements hematopoietic stem-cell transplant strategies while further safety and translational work proceeds.

Ending: Crocker said his lab will continue testing candidate immunomodulators and scaffold drugs for mutation-specific enzyme misfolding and called for multi-institutional efforts to evaluate repurposed therapies and their translational potential.