New Gene Therapy Approach Breaks Barriers for Treating Neurological Disorders

Researchers at the Broad Institute of MIT and Harvard have developed a promising gene delivery vehicle for treating brain diseases. Using a human protein, this vehicle effectively crosses the blood-brain barrier, delivering a disease-relevant gene to the brain in mice. The key lies in its binding to a well-studied protein in the barrier, suggesting potential efficacy in patients.

Gene therapy holds promise for severe genetic brain disorders lacking effective treatments. However, current methods face challenges in breaching the blood-brain barrier to deliver therapeutic cargo. Traditional vehicles like adeno-associated viruses (AAVs) struggle with this task, hindering the development of safe and efficient brain disease therapies.

The breakthrough comes from engineering the first published AAV targeting a human protein to reach the brain in humanized mice. By binding to the human transferrin receptor, highly expressed in the blood-brain barrier, this AAV surpasses existing methods. In mouse studies, it outperformed AAV9, an FDA-approved therapy, in delivering the GBA1 gene associated with various neurological disorders.

The implications are significant. Neurodevelopmental disorders, lysosomal storage diseases, and neurodegenerative diseases could all benefit. This advancement represents a milestone in enabling gene therapies for the central nervous system.

The approach marks a departure from traditional methods, which relied on animal testing to identify suitable AAV candidates. Instead, the team screened AAVs in a test tube for those binding to a specific human protein. This shift in strategy led to the discovery of BI-hTFR1, offering promising results across species.

Further development could enhance gene-delivery efficiency while reducing liver accumulation and antibody inactivation risks. Apertura Gene Therapy, a biotech company co-founded by one of the researchers, is already exploring therapies based on these findings.

This innovative gene delivery vehicle offers hope for treating challenging brain diseases, representing a significant step forward in the field of gene therapy.