New research shows that patients with childhood Batten disease have significant early-onset spinal cord disease, and that combined treatment of the spinal cord and brain has significant therapeutic effects.
The study entitled “Synergistic Effects of Spinal Cord and Brain Treatment in CLN1 Disease, â€Was published in the Proceedings of the National Academy of Sciences of the United States of America.
INCL (neuronal inflantile ceroid lipofuscinosis), also called infantile Batten disease, develops due to a deficiency in the enzyme PPT1. The researchers established mouse models lacking PPT1 to study this disease in animal models.
INCL was believed to be a consequence of a disease that only occurs in the brain. However, treating only the brain has been found to have very little beneficial effect in most patients, indicating that the disease can occur outside of the brain. Studies have also shown that mouse models of INCL exhibit deficits in their body’s motor and sensory pathways, suggesting that there may be a problem with the spinal cord.
Researchers from Washington University School of Medicine in St. Louis, Missouri, hypothesized that a component of the disease could occur in the spinal cord because it is central to sensory and motor pathways.
The researchers first showed that there was significant pathology in spinal cord disease using tissue obtained from children with INCL. Then, by examining the spinal cords obtained from mouse models of INCL at different ages, they showed early signs of disease in all parts of the spinal cord. In fact, these features of the disease appeared before the disease was seen in the brain.
This discovery prompted researchers to determine the therapeutic effect of treating the spinal cord. They used adeno-associated virus (AAV) mediated gene therapy, which is one of the most promising methods that have been shown to treat these types of diseases. In this type of gene therapy, a viral vector is used to deliver the deficient protein into the cells.
They administered two types of AAV injections to model INCL mice; one was injected into the spine and the other into the brain. The results of this study showed that targeting the spinal cord alone resulted in improvement of the disease.
Interestingly, the researchers showed that when gene therapy was given together in the brain and spinal cord, there was virtually no pathology of INCL in the brain or spinal cord. And by targeting both the spine and the brain, the INCL mouse model showed significant improvement in motor function and significantly longer lifespan.
The results of this study suggest that INCL starts in the spine and can be targeted to improve motor symptoms and lengthen patients’ lifespan.
“These data show that spinal cord pathology contributes significantly to the clinical progression of INCL and can be effectively targeted therapeutically. This has important implications for the provision of therapy in INCL, and potentially in other similar disorders, â€the authors concluded.
