About 100,000 of the estimated million people in the United States with multiple sclerosis (MS) have a progressive form of the disease, with symptoms that worsen continuously or after periods of remission.
"Progressive MS is profoundly challenging because it is relentless and treatment options are limited," said Francisco P. Gomez, a neurologist who specializes in MS and neuroimmunology.
MS is believed to occur when the immune system attacks the myelin sheath - the protective coating of the nerve fibers that transmit electrical impulses throughout the body - and disrupt this communication. The disease occurs more often in women, older people and those in northern latitudes.
Symptoms include fatigue, numbness or tingling, bladder and bowel problems and cognitive issues, but difficulty walking and balancing are the most common symptoms - and these are more pronounced in the progressive form of the disease. In addition, the progressive form is more prevalent among Black patients.
Now, Gomez and colleagues with the Texas A&M University Health Science Center (Texas A&M Health) have identified two estrogens that show promise in reducing the symptoms of progressive MS: estradiol and estriol.
For their study, published in the Journal of Neuroimmunology, the team evaluated estriol and estradiol as possible treatment protocols through a study that used a virus to mimic progressive MS.
"Testing potential therapies by using virus models of the disease is important because we recently learned that the Epstein-Barr virus contributes to the formation and development of MS by triggering an autoimmune response in susceptible individuals," said study author Jane Welsh, a neuroimmunologist with the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) and the Texas A&M Naresh K. Vashist College of Medicine.
She added that while women are more likely than men to develop MS, once they have the disease and become pregnant, they tend to go into remission.
"That's because during pregnancy - and especially in the third trimester - estradiol and estriol levels are elevated," said study author Candice Brinkmeyer-Langford, a neurogenerative disease expert with the Texas A&M School of Public Health. "Even women with MS who are on oral contraceptives experience fewer symptoms and have fewer relapses, so we evaluated how these hormones affect the myelin sheath."
Estrogen is a group of hormones that primarily affect sex drive and reproductive development, especially for women.
Estradiol is more potent than estriol and is used for hormone replacement therapy in postmenopausal women. Estriol, on the other hand, is used off-label for a variety of conditions and is FDA-approved only for treating urinary incontinence in dogs.
The researchers found that both types of estrogen decreased inflammation in the spinal cord, but only estradiol significantly decreased the damage to the myelin sheath, and believe this could aid in the development of therapeutic interventions for people with progressive MS.
Gomez, a graduate of the Vashisht College of Medicine, was with VMBS during the study period and is currently with the University of South Dakota Sanford School of Medicine. Others involved with the research were Colin R. Young, with VMBS; Farida Sohrabji, the Joseph Shelton Professor of Neuroscience at the Vashisht College of Medicine; and Shameena Bake, with the Vashisht College of Medicine. Welsh, Brinkmeyer-Langford and Sohrabji also are with the Texas A&M Institute for Neuroscience.
Genetic profiling offers hope for understanding multiple sclerosis risk