In his original career as a pharmacist, Samba Reddy says he frequently encountered female patients with epilepsy who complained that they had more seizures during their menstrual periods. He also noticed that neurologists prescribed the same medications for these women as they prescribed for men – and that the medications were largely ineffective.

After returning to school and earning a Ph.D. in pharmacology, Reddy set out to discover a better way to treat these women. In addition to developing new treatments, he is trying to understand the biological reasons why epilepsy affects men and women differently.photo of physician and patient looking at brain image

Reddy is among the faculty members in the Texas A&M College of Medicine who are involved with the Women’s Health in Neuroscience program, which was started by Farida Sohrabji, Ph.D., associate chair of the Department of Neuroscience and Experimental Therapeutics. Sohrabji saw a need for more basic research on how neurologic diseases such as epilepsy differ in men and women. The ultimate goal of the program is to learn how to exploit these differences to develop new therapies.

Reddy suspects that women are more prone to seizures around the time of menstruation – a condition called catamenial epilepsy – because the level of a key neurosteroid called allopregnanolone falls around this time.

“Because there is a hormonal component to this disorder, many neurologists don’t even know it exists,” Reddy says. “We are fundamentally ignoring the changes in brain receptors that women are going through.”

Reddy is developing a new paradigm for treating women with catamenial epilepsy that takes into consideration these hormonal changes. A key difference in this therapy, which he calls neurosteroid replacement therapy, is that women only have to take anti-epileptic drugs on a few key days each month rather than every day.

Reddy’s research on how hormonal cycles impact medication could have implications for other drugs that are given to women. For example, he says, the most commonly used sleeping medications, such as benzodiazepines, may work differently at various phases of the menstrual cycle. Migraine headaches offer another potential opportunity to expand Reddy’s research as those that occur around the time of menstruation are often harder to control with conventional medications.

Seizures and migraines aren’t the only afflictions that could factor into the battle of the sexes. Sohrabji’s research focuses on how a person’s age and sex impact their recovery from stroke.

“There are big differences in infarct volume (the amount of brain tissue that dies) as a result of age and sex,” Sobrabji explains. “Young women have the best response – with a very small loss of brain tissue – but males and older women have terrible responses.”

Sohrabji is particularly interested in trying to find a way to help middle-aged women recover from stroke.

“We are learning the hard way with stroke that drugs will work in one sex or the other, in one age group or the other, and in one ethnic group or the other, but there won’t be a one-size-fits-all treatment,” she says.

Many women who have strokes also develop post-stroke depression, and Sohrabji’s lab is one of only a few in the country that are studying this correlation in a pre-clinical model. Her team is trying to see if there are markers in the blood that will predict who is likely to develop post-stroke depression.

Sohrabji also is working with Reddy to study sex and age differences in post-stroke epilepsy. Twenty to thirty percent of people who have strokes develop epilepsy, and many of these patients are women. Sohrabji and Reddy are developing an animal model that will allow them to seek early markers for post-stroke epilepsy and test possible interventions.

“We can’t do anything about the stroke, but we can at least stop something else that is coming,” Reddy says.

A key goal of the Women’s Health in Neuroscience program is to train the next generation of scientists, who will further advance research into gender-specific medicine.

Min Jung Park, Ph.D., is among the postdoctoral research associates who are involved with the program, specifically the post-stroke epilepsy study.

“Like many other scientists, I had not considered gender as a biological variable,” Park says. “The Women’s Health in Neuroscience program offers me a unique opportunity to study how diseases present differently in men and women and apply those findings toward developing new drugs that are specific to women.”

Park notes that in the past, the dosage of drugs administered to women was either scaled up or down depending on their body weight, without giving consideration to the fact that there were physiological differences.

“I am very proud to be part of a program that has set out to fill this critical research gap,” Park says.

— Ellen Davis