A team from the Center for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC) and GeneT – Center of Excellence in Gene Therapy developed a new therapeutic approach for Machado-Joseph disease, a genetic and hereditary neurodegenerative disease also known as spinocerebellar ataxia type 3. This disease causes progressive deterioration of motor functions, affecting movements, speech, swallowing, and fine motor skills, without compromising cognitive and intellectual abilities. In Portugal, the disease has higher prevalence in the Azores, particularly on the island of Flores, where it can affect between one in every 140 and one in every 239 adults, and in the Central region.
The researchers used extracellular vesicles, small particles released by cells, to transport genetic editing tools to neurons. In these vesicles, they encapsulated the CRISPR-Cas9 system, managing to inactivate the mutant ATXN3 gene associated with the development of the disease. The approach is based on gene therapy, a type of treatment that involves editing DNA and opens possibilities for the cure of incurable rare genetic diseases.
The CNC-UC researcher and first author of the article, Kevin Leandro, explained that the goal was to understand if it would be possible to use extracellular vesicles to have a transient exposure to the genetic editing machinery and minimize unwanted edits. Extracellular vesicles overcome some limitations of conventional viral vectors, ensuring lower immune reaction, greater encapsulation capacity, and transient expression of the genetic editing tools.
The scientists also developed a light-controlled release system, using a photolabile protein, with the goal of increasing the efficiency of genetic editing. This proposal could contribute to new therapeutic strategies for Machado-Joseph disease.
