Terry Jo Bichell’s career path has moved her from training women in the developing world to breastfeed their newborn babies, to conducting neuroscience research to advance rare disease drug development. What’s strange about that is how logical a progression it’s been.

Bichell knew a thing or two about breastfeeding by the time her son Lou was born. Not only was she a licensed nurse and board-certified midwife, but she had four other children including twins she breastfed for three years.

When her son Lou had trouble feeding, she kept telling her pediatrician that there was something wrong, but the doctor dismissed it. Bichell said she told the physician she wasn’t communicating with the baby, but the doctor told her she was being neurotic. “It’s your first boy,” the doctor said, “and boys are different than girls.”

As Bichell and her husband continued to search for answers about Lou, a friend who was a geneticist looked at the baby over drinks and told the couple the child had facial characteristics consistent with a genetic disorder. The couple had a book about congenital malformations in newborns and had been flipping through the pages. Every time they came to the page about Angelman syndrome they would stop. The author of the book was a geneticist in the same town, and they reached out to him. He took one look at the happy and laughing child, placed a tuning fork on the 15-month-old’s knee, and watched him explode with laughter. He ordered a single test for Angelman syndrome, which confirmed the child had the condition.

Angelman syndrome is a neurological disorder. Children with the condition often smile, laugh, and are excitable. People with the condition have development delays, balance issues, motor impairment, and seizures. Some people with Angelman syndrome are unable to walk and most do not speak.

Bichell became a visiting scholar at Vanderbilt University and a co-investigator and coordinator of the Rare Disease Clinical Research Network. There she had access to researchers and would try to engage them on finding therapies for Angelman syndrome. There had been a few small trials to repurpose high-dose vitamins to treat the condition, but Bichell argued for a high-throughput drug screen to find potential treatments, something she couldn’t interest anyone in doing.

“Whenever I would talk to researchers and try to get them interested in looking at treatments, most of them felt that I was just crazy,” she said. “I realized that the only way I was going to be able to get some kind of a high-throughput drug screen done was to do it myself. And that would mean that I needed to just put my money where my mouth is and go back to school and just do it.”

That’s when Bichell decided to get a Ph.D. in neuroscience at Vanderbilt.

While she earned her Ph.D., the field advanced. Someone else conducted a high-throughput screen on known drugs to find potential candidates for Angelman syndrome.  And several promising antisense oligonucleotides emerged from labs.  

By the time Bichell graduated, though, she realized there was another need. While potential therapies were being identified, there wasn’t a good way to figure out how to measure whether those drugs work. Bichell was soon drafted to lead the Angelman Biomarkers and Outcome Measures Alliance (A-BOM), an effort by the Foundation for Angelman Syndrome Therapeutics and the Angelman Syndrome Foundation. That effort, which has involved patient organizations, academic institutions, and industry, has been a success. Bichell left the organization, but its work continues.

Now, though, Bichell is taking the A-BOM model and broadening it to include a wide number of genetic, non-verbal neurodevelopmental disorders and pooling efforts, studies, and data. She launched COMBINED Brain (Consortium for Outcome Measures and Biomarkers for Neurodevelopmental Disorders).

“We want to help these Angelman-like disorders pave the way to clinical trials by using similar wheels, not new wheels,” she said. “I’m against remaking wheels.”

Many of the people interested in seeing therapies for rare neurologic disorders face similar hurdles. They need help with natural history studies, they may lack an animal model for their disease, and may need to identify biomarkers and outcome measures for use in clinical trials.

Right now, COMBINED Brain is working to create a common data management system that could be shared across these disorders. It is also making sure the people running natural history studies are asking the right questions and working to ensure there is robust translational science that will allow potential therapies to advance to the clinic. The organization is also conducting a survey of the field to understand what biomarkers and outcome measures exist for severe neurodevelopmental disorders.

As with A-BOM, the model is to support the operational expenses of COMBINED Brain through membership fees. The base membership of the consortium consists of patient organizations, but COMBINED Brain is now expanding that to include academia and industry. Grants are expected to fund scientific work.

For now, Bichell has a lot on her plate, but she says she’s used to doing everything at once. Some things require the expertise of a neuroscientist and some things require a different skill set.

“I’m a mom of five kids,” she said. “I’m used to doing a lot of stuff.”

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