New gene delivery vehicle promises treatment for brain diseases

A study by scientists at the Broad Institute of MIT and Harvard University found that a gene therapy vector using human protein effectively crosses the blood-brain barrier and delivers a target gene into the brains of mice with human protein. This development could significantly improve the treatment of brain diseases in humans.

Gene therapy has the potential to treat severe genetic brain diseases for which there are currently no cures and limited treatment options. However, existing gene delivery methods, such as adeno-associated viruses (AAVs), are unable to effectively cross the blood-brain barrier and deliver therapeutic material to the brain. This challenge has hampered the development of safer and more effective gene therapies for brain diseases for decades.

Now, researchers in Ben Deverman’s lab have created the first published AAV that targets a human protein to deliver genes to the brain in mice with the human transferrin receptor. This virus binds to the human transferrin receptor, which is abundant in the blood-brain barrier in humans. In a new study published in the journal Science, the team showed that their AAV, injected into the blood of mice with the human transferrin receptor, entered the brain at much higher levels than the AAV used in the FDA-approved central nervous system gene therapy, AAV9. The virus also reached a wide range of important brain cell types, including neurons and astrocytes. The researchers also showed that their AAV was able to deliver copies of the GBA1 gene, which is associated with Gaucher disease, dementia with Lewy bodies, and Parkinson's disease, to a large number of cells in the brain.

The scientists suggest that their new AAV may be a better option for treating neurodevelopmental disorders caused by single-gene mutations, such as Rett syndrome or SHANK3 deficiency, as well as for lysosomal storage diseases such as GBA1 deficiency, and neurodegenerative diseases such as Huntington's disease, prion diseases, Friedreich's ataxia, and single-gene forms of ALS and Parkinson's.

"Since we joined the Broad Institute, our mission has been to create opportunities for central nervous system gene therapies. If this AAV meets our expectations in human studies, it will be much more effective than current methods," said Ben Deverman, senior author of the study.

The study also found that the new AAV could significantly enhance gene delivery to the brain compared to AAV9, which is approved for the treatment of spinal muscular atrophy in infants but is relatively ineffective for delivery of genes to the adult brain. The new AAV reached up to 71% of neurons and 92% of astrocytes in different brain regions.

Scientists believe that their new AAV development has great potential for the treatment of neurodegenerative diseases and can significantly improve the quality of life of patients.

The results were published in Science.