Brain interpretation: Scientists may be using new gene therapies to treat a variety of human brain diseases.

August 17, 2020 // -- A single gene mutation can trigger a life-changing disease and affect multiple systems of the body, such as dozens of lysosome storage diseases, which are caused by a single gene mutation that affects metabolism in cells. The production of key enzymes in molecules, which affect the function of multiple organs of the body, especially the brain, can cause varying degrees of intellectual disability, and gene therapy may be expected to treat these diseases, but the brain's own protective mechanism, the blood-brain barrier, has been a technical barrier for researchers.
recently, scientists from the University of Pennsylvania and others successfully applied gene therapy platforms to correct brain defects in large animal models of human genetic diseases in a study published in the international journal Brain entitled "Global CNS correction in a large brain model of human alpha-mannosidos by intravascular gene therapy".
researcher John H. Wolfe says it's the first animal model to have a human genetic disorder that exhibits intellectual disability (part of human syndrome) and now corrects bio-chemical and pathological damage throughout the brain; With the help of gene therapy, a viral transport vector could provide a normal version of the mutant gene to correct the disease, and now researchers have made some progress, or are expected to treat neurodegenerative diseases in rodents, but applying the same treatment to the larger brains of higher animals may only have the effect of partial disease correction.
Photo Source: CC0 Public Domain has seen a number of unexpected studies over the past decade or so, especially as special vectors can be injected into the blood and into the brain so that they can cross the blood-brain barrier, and a limited-distribution therapy may be effective in treating diseases that initially affect the body's spinal cord.
Now researchers have shown that these treatments can reverse the pathological performance of the entire brain in mice, but because the mesh cortical layer is much smaller than that of mammals such as humans, it is difficult for researchers to determine the effects of these treatments.
In the current study, researchers used an animal model very close to the brain and humans, the cat, which they hope will be used to assess the efficacy of gene correction therapy for a lysosome storage disease (alpha-mannosidossis), which often occurs in cats, caused by mutations in the alpha-glycoside storing gene.
more than a decade, researchers have been optimizing improved gene transport techniques, so they chose a special vector in the mouse study that can cross the blood-brain barrier and reach various parts of the brain.
The researchers were then able to transport the carriers carrying the reported genes to normal cats, and a few weeks later, they found evidence that the corrected genes could be distributed to various parts of the brain, including the cerebral cortical layer, the hippo horse and the middle brain.
The researchers then evaluated the cat with alpha-glycoside storage using a lower or higher dose of the vector, injecting therapy into the cat's cervical arteries so that it could reach the brain directly before reaching the rest of the body, with the treatment of animals with significantly delayed onset of specific neurological symptoms and longer lifespans than untreated cats, while those receiving higher dose vectors through the cervical arteries had the longest lifespan.
researcher Wolfe said: 'This may be a major advance, no researchers have been able to treat the entire brain of animals before, and we hope that the results of this paper will enter the human clinical trial phase in the future, of course, the results do not amount to a complete cure for human diseases.'
Researchers point out that while the symptoms of disease models can be significantly improved, they can only improve on serious diseases, cats are not actually cured, and researchers don't know how they affect the animal's mental abilities, and since pathological manifestations are found in the brain, it seems necessary to fully correct the disease.
However, since alpha-glycoside sepsis is an incurable disease in children, any way to reduce the severity of the disease is very popular with researchers, and in this study, the methods proposed by the researchers may also help treat other diseases that affect the entire central nervous system.
In future studies, researchers hope to improve current methods to effectively achieve the same therapeutic outcomes with lower dose vectors, and later researchers will continue to delve deeper into understanding the molecular mechanisms by which therapy works, including how therapeutic vectors reach the brain and whether other strategies can effectively address serious diseases in patients.
() Reference: 1 Sea Young Yoon et al. Global CNS correction in a large brain model of human alpha-mannosidosis by intravascular gene therapy, Brain (2020). DOI: 10.1093/brain/awaa161(2) Getting gene therapy to the brain.