Gene Therapy Reverses Symptoms of Rare Neurological Disease in Animal Mdels

Rare Daily Staff

A new study demonstrates the potential for a gene therapy to restore motor capacity in the ultra-rare disease megalencephalic leukoencephalopathy with subcortical cysts, even when treatment begins after symptom onset, a new study reports.

The study, published in Molecular Therapy, represents “a significant breakthrough, as it suggests that gene therapy could be effective even in advanced stages of the disease”, said Alejandro Brao, researcher at the Department of Biochemistry and Molecular Biology at Universitat Autònoma de Barcelona and first author of the article.

The researchers said the findings could open new therapeutic avenues for MLC patients and highlight gene therapy’s promise in treating rare neurological diseases by restoring affected gene expression. The study was conducted by researchers at Universitat Autònoma de Barcelona in collaboration with researchers from Raúl Estévez’s group at the Bellvitge Biomedical Research Institute.

Megalencephalic leukoencephalopathy (MLC) is a rare childhood neurological disorder that primarily affects the brain’s white matter. It is characterized by macrocephaly, impaired motor coordination, and epilepsy, among other symptoms. More than 75 percent of diagnosed cases are caused by mutations in the MLC1 gene, which encodes a protein located in the membrane of a type of brain cell called astrocyte. This protein plays a key role in regulating water and ion balance in the brain, but its exact function is still not well understood.

Researchers administered a viral vector carrying a healthy copy of the MLC1 gene to an animal model of the disease in order to restore normal protein activity. The results confirmed the effectiveness of the treatment, as gene expression was maintained in the brain for a year, normalizing physiological brain alterations and reversing motor impairments in treated mice.

The researchers said the next steps will focus on identifying the most suitable gene therapy vector for clinical application, determining the minimum effective dose, and conducting biosafety and biodistribution studies in larger animal models.

Photo: Research team from Universitat Autònoma de Barcelona