Estriol Plus Copaxone May Protect Against Nerve Damage in RRMS
Taking the pregnancy hormone estriol in combination with Copaxone (glatiramer acetate) significantly reduced the blood levels of neurofilament light chain (NfL) — a marker of nerve damage — in women with relapsing-remitting multiple sclerosis (RRMS), clinical trial data show.
These lower NfL levels were significantly associated with a reduced brain lesion volume, a sign of MS-related tissue damage.
“In this head-to-head comparison, estriol + [Copaxone] treatment reduced [blood] NfL as early as 12 months, while placebo + [Copaxone] did not,” the researchers wrote.
These findings were consistent with estriol-mediated protection from nerve cell injury and further support the use of NfL as a biomarker in MS, the team noted.
The analysis was published in the Annals of Clinical and Translational Neurology, in a study titled “Decreased neurofilament light chain levels in estriol-treated multiple sclerosis.”
Estrogens are a group of female hormones that have been shown to have protective properties in some neurodegenerative conditions. Estriol, one of three major estrogens, is produced during pregnancy — a period in which multiple sclerosis disease activity is reduced — with levels in the bloodstream rising throughout gestation.
In a previous two-year study, researchers at the University of California investigated the impact of oral estriol, combined with the approved MS therapy Copaxone, on relapse frequency. That Phase 2 clinical trial (NCT00451204) involved 158 women with RRMS.
Results showed that the pregnancy hormone tended to reduce the annualized relapse rate, lessen fatigue, improve cognition, and slow brain volume loss — but these changes were not statistically significant compared with those seen in patients receiving Copaxone plus a placebo.
Because estriol treatment slowed brain loss volume after one year, the team conducted a new analysis of blood samples collected during the trial to determine estriol’s effect on NfL levels, a known biomarker for nerve fiber damage and loss.
Blood samples were available for 111 participants, ages 20–54. Among them, 62 had received 8 mg of oral estriol daily plus Copaxone, and 49 were given a placebo alongside Copaxone. Researchers measured NfL levels before treatment (baseline) and after six and 12 months.
The analysis showed that blood estriol levels at six months and one year were significantly higher in those given estriol compared with patients given the placebo. In fact, the levels in treated participants matched those seen during the late second to the early third trimester of pregnancy. Meanwhile, the placebo group had estriol levels at the lower limit of detection, similar to nonpregnant women.
After 12 months, patients in the placebo group had experienced no changes in their NfL levels, but this biomarker had significantly dropped in the estriol group. Additional statistical analyses showed that reduced NfL levels after estriol were significantly associated with a decrease in the volume of brain lesions.
Reductions in NfL levels, however, were not associated with changes in MS severity or relapse rates, changes in brain volumes, or changes in gadolinium-enhancing lesions — areas of damage with active inflammation.
“Here, oral treatment with an estrogen unique to pregnancy (estriol) using an 8 mg dose to induce a mid-pregnancy blood estriol level reduced serum neurofilament light chain in nonpregnant MS women,” the researchers wrote.
These results were “consistent with estriol-mediated protection from neuro-axonal injury and supports the use of serum neurofilament light chain as a biomarker in MS,” they concluded.