As a leading researcher of rare diseases that affect children’s brains, Jonathan D. Cooper, PhD, thought little about the gastrointestinal (GI) system. That is, until the parents of children with a condition that Cooper studies urged him to investigate why debilitating digestive issues troubled their kids, who suffer from an incurable and fatal neurodegenerative brain condition called Batten disease.
Doctors had informed the parents that their children could succumb to blindness, seizures, dementia, an inability to walk, and would die in childhood. But the parents told Cooper they felt unprepared for the severe constipation and intestinal problems their kids also experienced.
“We are all miserable when we can’t poop,” said Cooper, a professor of pediatrics, of genetics and of neurology at Washington University School of Medicine in St. Louis. “It can be painful and a serious quality of life issue for the child and their families.”
The parent perspective led Cooper on a scientific quest that began four years ago — and continues today — to study the half-billion nerve cells in the bowel wall that are part of the enteric nervous system and how Batten disease affects their function. His new work shows enteric neurons in two mouse models of Batten disease degenerate in the bowel, paralleling neurodegeneration long known to occur in brain and spinal cord.
Cooper’s prior research also showed that supplying the missing enzyme to the brain in mouse or sheep Batten disease models via enzyme replacement therapy slowed cellular degeneration. Now his latest study has found that gene therapy in mice produced the same protective effect in the bowel. This genetic treatment reduced bowel symptoms and extended the lifespan of the mice by preventing enteric neuron degeneration.
The findings, published Jan. 15 in Science Translational Medicine, may one day lead to new treatments for Batten disease as well as for other neurodegenerative disorders with gastrointestinal symptoms.
“We believe our studies in mice have demonstrated a novel and highly promising way to successfully treat GI conditions with gene therapy,” said Cooper, the study’s co-senior author. “Importantly, we also established that the GI issues were not secondary to the neurological changes in the brain or spinal cord caused by the disease, but happen in the bowel itself.”