Bedside to bench to bedside research: Estrogen receptor beta ligand as a candidate neuroprotective treatment for multiple sclerosis

- MS protection during pregnancy led to clinical trials of estriol treatment in MS.
- Estrogen receptor (ER) beta ligand could be a “next generation estriol” treatment.
- ER beta ligand treatment is neuroprotective in spinal cord and brain in EAE.
- ER beta ligand treatment spares gray matter atrophy on longitudinal in vivo MRIs.
- Treatment preserves not only myelin and axons in WM, also neurons and synapses in GM.

Protective effects of pregnancy during MS have led to clinical trials of estriol, the pregnancy estrogen, in MS. Since estriol binds to estrogen receptor (ER) beta, ER beta ligand could represent a “next generation estriol” treatment. Here, ER beta ligand treatment was protective in EAE in both sexes and across genetic backgrounds. Neuroprotection was shown in spinal cord, sparing myelin and axons, and in brain, sparing neurons and synapses. Longitudinal in vivo MRIs showed decreased brain atrophy in cerebral cortex gray matter and cerebellum during EAE. Investigation of ER beta ligand as a neuroprotective treatment for MS is warranted.