动物实验,基因治疗 z-bo 2020-10-13 389

　　Among 100,000 babies, a mutation in the GALC gene in one baby can cause an incurable and fatal disease, namely baby club disease or glomerular leukocyte malnutrition. Most children with this disease die before the age of two.

　　Parallel diseases also naturally affect dogs. They usually show symptoms of the disease at 6 weeks of age and die within a few months. A study conducted by the Journal of Clinical Investigation (JCI) led by Charles Vite of the School of Veterinary Medicine described effective gene therapy that can effectively treat and maintain the effects of Kraff’s disease in dogs. The treated dog is over 4 years old and has no obvious symptoms. This work highlights the possibility of similar treatments for children. The lead author of the new study, Witte's professor of neurology, said: "There is no good cure for this disease." "We have been studying this disease in dogs since the 1990s, but it is actually Xiangxin. The transfer of American gene therapy vectors gives us the opportunity to treat diseases that have a major impact on the nervous system." Kreb's disease is a type of lysosomal storage disease in which cell-specific substances are accumulated in the enzyme itself. In a small container. Generally, the GALC gene encodes an enzyme that can break down lipids in the body. In Clave disease, the mutated GALC causes lipid accumulation, leading to the growth and deformation of the lipid-containing coating of nerve cells (myelin sheath), which leads to impaired nerve cell signaling. As a result, children with Kraff’s disease experience progressive neurological symptoms such as blindness, hearing loss, and paralysis. A one-month-old bone marrow transplant can prevent about 30% of babies from developing symptoms, but this method is very risky. Witte said: "We really need a new treatment." Cliff's disease was one of the first children to discover a genetic disease similar to dogs. Dogs with this disease are part of the Penvet Human Genetic Disease Animal Model Center, where new treatments can be researched. In order to inactivate the effects of this disease, researchers know that it is important to introduce a healthy version of the GALC gene into the brain. They have made progress by providing the GALC gene AAV9 vector, which has been effectively used for experimental gene therapy of other neurological diseases using specific vectors and seems to be the best candidate for FDA approval.

　　The place of delivery is also very important. Witte said: "We decided to inject spinal fluid from the back of the head, which is the most effective way to enter the brain." Researchers used both high-dose and low-dose gene therapy to treat neurological symptoms two weeks before the onset of symptoms.

　　Vite and others worry that providing a regular copy of GALC may not completely relieve symptoms. This is partly due to the formation of the toxic compound psychotic protein produced by the metabolism of the mutant GALC enzyme. But the team was excited about such an amazing result.

　　Dogs receiving high-dose gene therapy before the onset of symptoms not only have healthy brain sheath formation, but also maintain peripheral nerve sheath formation. Witte said: "This is a big surprise for us. Injecting gene therapy into spinal fluid can have a positive effect on the central and peripheral nervous system, which is very exciting." The dog also has no symptoms. More than 4 years.

　　Dogs who receive treatment even after they develop symptoms have a longer life span compared to not using this treatment. However, low-dose gene therapy has led to an intermediate form of the disease, emphasizing the importance of accurately indicating the correct dose when communicating findings to children. Allison Bradbury, a former postdoctoral researcher at Vite, the lead author of the "JCI Paper", is now a researcher at the National Children’s Hospital, and will continue this work to understand systemic therapy.