Oct. 15, 2025
Rare Optimism
A Pitt researcher's decades of investigations leads to a potential treatment for a child with a rare genetic disorder.
TOPICS: Aging & Lifespan | Basic Science | School of Medicine
By Andrew Doerfler
When Marisa and Shane Trani learned that their daughter, Kelsey, had PACS1 syndrome—an ultra-rare, genetic neurodevelopmental disorder—they were told that effective treatment could be years away.
Kelsey had spent her young life dealing with heart trouble, difficulty eating and swallowing, low muscle mass, weak retinas, developmental delays and other challenges. A difficult series of emergency room stays and an avalanche of questions eventually led to her diagnosis.
When they wanted to learn more about ongoing research and future therapies, their physician suggested they contact Gary Thomas, professor of microbiology and molecular genetics at the University of Pittsburgh School of Medicine.
Thomas had led the discovery of the PACS1 gene in 1998. Years later, other researchers found that in people like Kelsey, the gene is mutated, which dysregulates the trafficking of proteins that are important to the development of nerve cells.
In the United States, conditions that affect fewer than 200,000 people are considered rare diseases, 80% of which are genetic. Even though each of these is rare on its own, taken together they affect about 30 million people in the United States, according to the National Institutes of Health—about 1 in 10 people has one. Yet of the 7,000 rare diseases with a known molecular cause, only 500 have an approved treatment.
For PACS1 syndrome, the Tranis had learned about an experimental treatment that used antisense oligonucleotide (ASO) therapy. It could target the expression of the very gene that was throwing Kelsey’s system into disarray.
But the chance Kelsey could receive the therapy herself seemed remote to the Trani family, until they got in touch with Thomas.
With the new treatment, the family and their doctors are hopeful Kelsey will have "the best chance possible at an independent life," Marisa Trani says.
In October 2023, with collaborators at the biotechnology company Ionis, Thomas was the senior author on a paper that showed that ASOs could restore neuronal structure and synaptic transmission in mice.
After meeting the Trani family, who live in Virginia, Thomas worked with clinicians and administrators at Pitt and UPMC to see if they could treat Kelsey. They connected with n-Lorem, a nonprofit started by the founder of Ionis, that provides ASO therapies to patients with ultra-rare diseases at no cost.
The Trani family soon learned that n-Lorem had recommended Kelsey for ASO therapy. With the new treatment, the family and their doctors are hopeful Kelsey will have “the best chance possible at an independent life,” Marisa Trani says.
Thomas and his collaborators at Pitt already have their sights set on expanding Pitt’s ability to help more PACS1 syndrome patients. He plans to set up a fund at UPMC Children’s Hospital Foundation that individuals and organizations can donate to in support of the effort.
“When you think about it from the bigger, the macroeconomic picture, having a kid less ill, more healthy, is definitely going to be a lot less costly to society in general,” Thomas says. “And their life is improved enormously.”