Drug Target for Rare Disease

Drug Target for Rare Disease

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, dominantly inherited, neurodegenerative disorder caused by mutations in the receptor (CSF-1R) for the growth factor CSF-1. There are no available treatments for ALSP patients, who generally die within 5 to 7 years of the appearance of disease symptoms.

In a study of the mouse model of ALSP published online on March 3 in Cell Reports, E. Richard Stanley, Ph.D., and colleagues report the elevation of another growth factor, CSF-2, in the brains of both ALSP mice and patients. Both CSF-1R and CSF-2 regulate microglia and the paper shows that reducing levels of CSF-2 attenuates ALSP development in the mouse. In addition, the authors report that reductions in CSF-2 also impair functioning of microglia and of the aging central nervous system, indicating that balancing CSF-1R/CSF-2 signaling is necessary for homeostasis. Because increased CSF2 levels and decreased CSF-1R expression have also been reported in Alzheimer’s disease and multiple sclerosis, the authors suggest that the unbalanced CSF-1R/CSF-2 signaling contributes not only to ALSP, but also to other neurodegenerative conditions.

Dr. Stanley is professor and chair of developmental and molecular biology and holds the Renée E. and Robert A. Belfer Chair in Developmental Biology at Einstein.

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