Gene therapy reverses symptoms of rare neurological disease in animal models

A recent study led by the Universitat Autònoma de Barcelona (UAB) demonstrates the potential of gene therapy to restore motor capacity in an ultra-rare disease, Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC), even when treatment begins after symptom onset.

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% 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.

In this research, a team led by Assumpció Bosch from the Department of Biochemistry and Molecular Biology and the Institut de Neurociències of the UAB (INc-UAB) 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 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", explains Alejandro Brao, researcher at the Department of Biochemistry and Molecular Biology and INc-UAB, and first author of the article.

"Our 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", added Assumpció Bosch, coordinator of the study.

These research findings have the potential to open new therapeutic avenues for MLC patients while also showcasing the promise of gene therapy in treating rare neurological diseases by restoring the expression of affected genes.

The study was conducted in collaboration with researchers from Raúl Estévez’s group at the Bellvitge Biomedical Research Institute.