动物实验,基因疗法 z-bo 2020-11-05 344

　　Researchers from the University of Tokyo in Japan used the DOK7 gene therapy method to successfully treat two neuromuscular diseases by increasing the neuromuscular junction that transmits brain signals to the muscles.

　　In this study, the virus carrying the therapeutic gene entered the cell to enhance the performance of the mouse muscles, improve motor skills, and prolong the lifespan of the mice suffering from two neuromuscular diseases. The researchers said this discovery is expected to help a class of people with similar diseases, including muscular dystrophy and amyotrophic lateral sclerosis (ALS).

　　Many diseases are related to neuromuscular junction defects. Neuromuscular junctions are the physical connections between nerves and muscles. They are also the parts that receive signals from the brain to contract muscles.

　　Familial limb girdle muscle weakness

　　Familial limb-girdle myasthenia (familial limb-girdle myasthenia) patients usually carry two defective copies of the DOK7 gene. These patients have muscle atrophy in the hips and shoulders. Some of these patients eventually have difficulty breathing and die in a wheelchair. In the same way, mice with DOK7 unable to work properly lost weight and died within a few weeks.

　　In this study, a research team led by molecular biologist Yuji Yamanashi injected a non-toxic virus carrying a normal copy of the DOK7 gene into DOK7-deficient transgenic mice for the first time. After about 7 weeks, the muscle cells of these mice expressed DOK7 protein, and microscopic observation revealed that their neuromuscular junctions were larger than those of untreated mice. In addition, the weight of the mice increased to a healthy level, motor skills and muscle strength tests were normal.

　　Emery-Dreifuss Muscular Dystrophy

　　With the above research results, the researchers want to know that DOK7 gene therapy can work in mice with other muscle-related diseases. The researchers chose another mouse model, Emery-Dreifuss muscular dystrophy (EDMD), a human genetic disease related to muscle protein gene defects, which can also cause neuromuscular junction abnormalities and muscle weakness. After DOK7 gene therapy treats mouse models of these diseases, the mice live longer, have larger neuromuscular junctions, and exercise test results are stronger than untreated mice.

　　However, there is a significant difference in the therapeutic effect of DOK7 gene therapy on these two disease mouse models. EDMD mice are still skinny after treatment. The researchers analyzed that this may be because genetic defects in EDMD mice have also caused heart disease, and DOK7 gene therapy has no therapeutic effect on this. People with EDMD usually need a pacemaker.

　　Application prospects

　　Researchers believe that DOK7 gene therapy may also be used for other neuromuscular diseases related to abnormalities of neuromuscular junctions, but not necessarily due to DOK7 mutations. Currently, they are studying the use of DOK7 gene therapy to treat other diseases, as well as testing on larger animals.

　　University of Washington muscle disease researcher Martin Childers pointed out that most gene therapy for neuromuscular diseases is to correct a specific defective gene. However, these diseases are usually caused by hundreds of gene mutations. Therefore, scientists can try to combine different gene therapies to find the best combination to treat neuromuscular diseases.