Five-year-old Hadley Jo Brindley has an extremely rare disease and an extremely determined set of parents and hometown supporters in Bowling Green, KY. And thanks to the funds they have raised, a scientist at Cincinnati Children’s is making significant progress in his quest for a cure.
In the span of just five years, a mitochondrial disorder known to affect only a few dozen people in the world has moved from discovery to early signs of success for a potential gene therapy. Details of the work, led by Taosheng Huang, MD, PhD, and colleagues were published Jan. 16, 2020, in the journal Human Molecular Genetics.
“We know it’s still too early to know if all of this will help Hadley, but I do believe God put us with Dr. Huang,” says Ashley Brindley, Hadley Jo’s mother. “We’re not only helping Hadley but other children and adults too that are suffering with this.”
“This” is a condition so uncommon it has more of a label than a name: hereditary motor and sensory neuropathy, type VIB—also called HMSN6B for short. In essence, a malfunction in Hadley’s mitochondria—the energy-processing component of all our cells—is gradually affecting her eyesight, limiting her ability to walk, and interfering with her brain development.
Just having the condition diagnosed was an enormous challenge for the family.
Twisting Road Leads to Cincinnati Children’s
Hadley Jo seemed healthy when she was born in May 2014. But during her first year, she started missing milestones. Her parents Ashley and Casey began to notice that she was having difficulties learning to walk and abnormalities in her eye movement.
When they brought Hadley in for an 18-month check-up, their pediatrician referred the family to an optometrist. Upon seeing Hadley Jo’s delayed motor skills, the optometrist referred the family to a pediatric ophthalmologist at Vanderbilt Children’s Hospital, about 70 miles south in Nashville, TN.
There, an MRI scan quickly detected abnormalities in Hadley Jo’s cerebellum—the “little brain” near the brain stem that controls most motor skills. This explained why she was having difficulty walking, but it took another year of testing to determine that Hadley Jo had a gene “error” that none of the experts at Vanderbilt had seen before, her mother Ashley says.
This was an alarming situation because Vanderbilt is nationally known as a high-quality medical center. Ashley was unsure what further steps could be taken, but she had no plans to stop taking steps.
“Me being the type of person that I am, I decided to see what I could find on the internet,” Ashley said.
The hunt required wading through dense scientific references like the information posted by the “Online Mendelian Inheritance in Man,” a genetics library created by Johns Hopkins University as a tool for genetic researchers and advanced medical students. But the work paid off.
“I saw that Dr. Huang was doing research on this. So, I reached out to their team, told them our story and asked if they’d be willing to meet with us. They said ‘yes’ pretty much immediately,” Ashley says.
After talking in December 2016, the family drove about 225 miles north to Cincinnati in February 2017 for Hadley’s first visit with Huang and his team.
Even Without a Cure, an Answer and a Call
Ashley had learned on her own that Huang was a noted authority on mitochondrial disorders. In fact, he was the co-corresponding author of a 2015 research paper that reported discovering a gene mutation that produced symptoms closely matching Hadley Jo’s experience. The other co-corresponding author was Stephan Zuchner, MD, PhD, at the University of Miami in Florida.