Prozac trial to assess prenatal treatment of Down syndrome

By Elizabeth Bacharach

Paul Watson is a father, a husband and a Southwest Airlines pilot.

But as an explorer, he searches each city he lands in for the labs of local scientists studying Down syndrome.

He’s also the “ideas man” behind the first human trial to test fluoxetine, also known as Prozac, as a prenatal treatment for Down syndrome.

But why is a pilot from Georgia so dedicated to the search for a treatment for Down syndrome?

Meet Nathan, Watson’s 14-year-old son who has the condition, a genetic disorder that occurs when an individual has a full or partial extra copy of chromosome 21.

Individuals with Down syndrome can experience intellectual impairments such as lower IQ. Studies link the impacts to abnormal brain development caused by impairment of neurogenesis, the process of the creation of neurons.

Down syndrome currently lacks a cure or definite drug treatment.

Four years ago, Watson sought his pediatrician’s advice about starting Nathan on Prozac—in addition to other supplements— after reading studies on mice with the genetic equivalent of the disorder that found positive effects from treatment using the antidepressant.

Although he said he can’t attribute any specific changes in Nathan directly to Prozac and thinks it may be too late for the drug to “make a difference cognitively,” Watson continues to support this treatment for his son. “it’s just kind of a hope that it’s going to do something,” he said.

Watson, however, wants to do more than just “hope.”

After reading a study in the journal Brain  that showed reversal of the cognitive and behavioral challenges of Down syndrome in unborn mice treated with fluoxetine, Watson contacted Dr. Matt Byerly. He met Byerly a year earlier after following the psychologist’s work at the Center for Autism and Development Disabilities at the University of Texas Southwestern Medical Center. Watson suggested a similar study in humans.

“I felt that the article in combination with the other Down syndrome mouse-model studies of fluoxetine now suggested that we should actually do a prenatal study rather than a young-child study,” Byerly said. “The disturbances associated with Down syndrome are considerably present by birth and so waiting after birth would miss a potential large opportunity to aid brain development in Down syndrome.”

That was in January 2014.

By May 2014, Byerly, who recently moved to the University of Montana but is still involved with the trial, received $75,000 in university funding from UT Southwestern. And Watson and other donors  contributed another $85,303 raised through a group fundraiser on CrowdRise, a platform dedicated to charitable giving.

The trial will include 21 pregnant women whose babies tested positive for Down syndrome through prenatal genetic testing. Fourteen will be chosen randomly to take fluoxetine and seven will receive a placebo. Neither group will know what their assigned medication actually was until the study is complete.

Treating fetuses with any drug is unusual, and although fluoxetine is over 27 years old, studies have linked the drug with small risks of serious lung and heart problems in unborn babies and an increased risk of autism.

Mothers involved in the study will be fully informed about the potential side effects of Prozac and must provide their informed consent to participate.

According to Byerly, the team at UT Southwestern detailed the risks of administering fluoxetine to pregnant women to the Institutional Review Board (IRB), and the conclusion was that “while there was the potential for some side effects, that they are relatively rare.”

Byerly added that the IRB and study team decided that the possible benefit for individuals with Down syndrome achieved through the study outweighed the potential risks.

During the prenatal portion of the study, a participant will take their assigned medication until her child is born. After birth, the child will begin taking the assigned medication for two years, during which he or she will be continuously evaluated.

“The overall project is really a collaboration between the obstetrics group…and the psychiatry department,” said Dr. Carol Tamminga, chair of the psychiatry department at UT Southwestern and head of the study.

The pilot study is a preliminary trial involving a small group of patients to evaluate accessibility and feasibility of this treatment and the preliminary results to evaluate the need for a more comprehensive test.

Throughout the test, the team will be comparing the prenatal brain formation and function to formation and function after birth through magnetic imaging, such as MRI’s. And ultimately, the doctors will compare the children’s developmental functioning between the fluoxetine-treated group and the control group. To assess results, the UT Southwestern team will look at and compare both the brain studies achieved through the images and the children’s’ results of neurodevelopmental tests taken as toddlers.

“Our goals are to try to improve the cognitive function in children, as they would grow through adults such that they can obtain a higher level in functioning and quality of life,” Byerly said.

However, Dr. Diana Bianchi, a human medical geneticist at Tufts University Medical School, said that “well-validated studies” have shown potential fetal risks associated with Prozac.

“There are some concerning aspects of giving Prozac prenatally to women who need it because of their own psychiatric disorders,” said Bianchi, who is not involved in the trial.

Dr. Robyn Horsager-Boehrer, one of the study co-investigators and an obstetrician who specializes in high-risk obstetrics, said she thinks the drug’s safety profile is good enough to justify the unusual step. “This is a drug that, if a woman came to me and had depression, I would not counsel her to stop taking during pregnancy,” she said.

Tamminga sees benefits for both mothers and babies. “I felt that there was every mother in America who had the possibility of having a Down syndrome child that was really looking to important data like this to answer the question, ‘is there a treatment?’ There’s no treatment at all for Down syndrome, and it really seemed imperative that we follow through with it.”

The UT Southwestern trial team will start recruiting participants. Tamminga said they plan to begin the study in May.

Photo at top: Preliminary screening tests for Down syndrome include ultrasound and take place between 10 and 20 weeks of pregnancy. (Elizabeth Bacharach/MEDILL)