Multipronged approach distinguishes gene function changes that promote Parkinson’s disease from those that confer protection

HOUSTON – (April 23, 2026) – Researchers at Texas Children’s Hospital’s Duncan Neurological Research Institute (Duncan NRI) and Baylor College of Medicine (Baylor) have developed a novel strategy that combines computational and experimental approaches to distinguish gene function changes that contribute to Parkinson’s disease from those that protect against it.

The study, published in Neurobiology of Disease, identifies new risk factors and previously unrecognized therapeutic targets, offering hope for future treatments that could prevent, slow, or stop this devastating condition.

“Parkinson’s disease is the most common neurodegenerative movement disorder, affecting more than 10 million people worldwide,” said corresponding author Dr. Juan Botas, investigator and director of the High Throughput Behavioral Screening Core at the Duncan NRI and Professor at Baylor. “Current therapies can help manage symptoms, but they do not prevent the progressive loss of neurons that drives the disease.”

A defining feature of Parkinson’s disease is the buildup of a protein called alpha-synuclein inside neurons. In healthy cells, this protein is continuously produced, used, and recycled. In Parkinson’s disease, this recycling system fails, leading to toxic accumulation—particularly in dopamine-producing neurons that are essential for normal movement.

Identifying harmful vs. protective gene changes
“Our goal was to better understand which gene changes contribute to disease and which may actually protect against it,” said first author Justin Moore, graduate student in the Botas lab. “Some changes may worsen disease, while others may represent the cell’s natural defense mechanisms.” Distinguishing these roles is critical for developing effective therapies. Targeting harmful gene activity could help slow disease progression, while enhancing protective pathways could provide new treatment strategies.

A combined computational and experimental strategy
The team first used advanced computational methods to integrate large-scale datasets—including genetics, gene expression, and protein data—from both human samples and model systems. This allowed them to identify networks of genes consistently altered in Parkinson’s disease.

They then tested these gene networks in a well-established fruit fly model engineered to produce human alpha-synuclein. These flies develop movement impairments and neuron loss similar to key features of Parkinson’s disease.

“We were particularly excited by what we found,” Botas said. “Genes involved in cellular recycling and waste-disposal pathways can either worsen or reduce disease features. Importantly, modifying specific genes—such as STAM1/2, INPP4A/B, and TMEM55A/B—improved movement, reduced neurodegeneration, and protected dopamine-producing neurons.”

Toward new therapeutic strategies
These findings provide new insight into how Parkinson’s disease develops, highlighting the importance of the cell’s internal recycling systems. The study demonstrates that it may be possible to alter the course of the disease by reprogramming these pathways. “This work moves us closer to identifying therapies that not only treat symptoms but target underlying disease mechanisms,” Botas said.

Researchers contributing to this study were based at Texas Children’s Hospital, Baylor College of Medicine and collaborating academic institutions.

This work was supported by the Huffington Foundation and the National Institutes of Health.