Gene therapy repairs neural connections in mice with Hurler syndrome

The University of Minnesota has released a pioneering study detailing the potential of gene therapy to repair neural connections in patients with the rare genetic brain disorder, Hurler syndrome. This groundbreaking research suggests the possibility of adopting gene therapies as a new standard of treatment for disorders like Hurler syndrome, which has a profound impact on affected individuals.

About Hurler Syndrome:

Hurler syndrome, scientifically known as mucopolysaccharidosis type I (MPS I), is a genetic disorder observed in newborns. It causes severe cognitive deficiencies and physical abnormalities. The root cause is genetic mutations that disrupt the synthesis of the vital lysosomal enzyme IDUA, leading to progressive brain damage. Tragically, those affected often face death by age 10. Present treatments, which include perilous bone marrow transplants and continuous enzyme replacement, fail to halt the advancing brain damage.

Research Details:

U of M scientists evaluated a novel gene therapy called the PS gene-editing system, created at the university itself, using mice with Hurler syndrome. This technique generated high and consistent levels of normal enzymes in the liver that could reach the brain through the circulatory system. Using advanced resting-state functional MRI (rs-fMRI), researchers first identified disrupted neural networks. They then gauged the recovery of brain function and connectivity post-gene therapy.

Significant Findings:

The innovative PS gene-editing technique yielded normal enzymes that preserved normal connections within distinct neural networks.

High-resolution rs-fMRI brain connectome imaging technology, crafted by Wei Zhu, played a crucial role in the discovery.

Expert Insights:

Walter Low, a leading author and professor at U of M Medical School, expressed his enthusiasm by labeling the research a breakthrough. He emphasized its importance by highlighting it as the first gene therapy instance that successfully treated a neurological disorder and restored brain connectivity, as validated by rs-fMRI.

Wei Chen, another prominent author, indicated the potential of translating this approach to real-world clinical scenarios, especially for genetic brain disorders. Chen accentuated the significance of being able to continuously produce the normal IDUA enzyme in the liver and its ability to cross the blood-brain barrier to rectify brain abnormalities.

Perry Hackett, co-author and professor, anticipates this new approach’s broader applications, specifically in monitoring brain connectivity in other lysosomal disorders impacting brain function post-gene editing.


The study saw contributions from multiple experts, including Lin Zhang, Ying Zhang, Xiao-Hong Zhu, Isaac Clark, and Li Ou, among others.


This groundbreaking work was backed by several National Institutes of Health Grants, the Susanne M. Schwarz Fund, and the Hackett Royalty Fund.