Madison Reporter

Researchers at the University of Wisconsin–Madison have made progress in using gene therapy to treat hereditary neurodegenerative diseases in rats. The study, led by Professor Anjon Audhya, focuses on hereditary spastic paraplegia (HSP), a group of movement disorders that cause progressive weakness and stiffness in the legs due to inherited genetic mutations.

Using CRISPR-Cas9 genome editing technology, Audhya's team developed a rat model with a mutation in the Trk-fused gene, which is linked to HSP. This gene typically helps transport proteins within neurons, and its disruption leads to symptoms of weakness and stiffness.

The researchers introduced a genetically engineered virus into day-old rats' brains. This virus carried a normal version of the Trk-fused gene to compensate for the mutated one. "Those animals never got disease," says Audhya. "So they were able to live for many, many additional weeks, never showing signs of disease."

Their findings suggest that HSP is primarily a disorder affecting neurons rather than other brain cells like astrocytes. The study was published in the Proceedings of the National Academy of Sciences.

Audhya's team plans further studies targeting different gene mutations more common among HSP patients and aims to administer treatments via the spinal cord. Funding from Blu Genes Foundation, The Lilly and Blair Foundation, CureSPG4 Foundation, and National Institutes of Health has been crucial for their research.

"We ultimately hope our preclinical gene therapy efforts will lead to a new clinical trial in patients in the years to come," Audhya states.