Yesterday, the journal Cell, one of the world’s three largest scientific journals, published a weighty paper online. (Vieira et al., Jagged 1 Rescues the Duchenne Muscular Dystrophy Phenotype, Cell (2015)) The paper starts with two rare dogs with very mild disease (named Ringo and Sulfair, respectively) in a DMD dog model (GRMD Golden Retriever) and finds that Dystrophin is completely absent in the muscle cells of these dogs with very mild disease, meaning that the apparent improvement in disease is not due to The apparent improvement was not due to the re-expression of Dystrophin protein. The dogs with minimal disease still had significantly elevated blood muscle enzymes and muscle biopsies still had significant dystrophin-like changes. However, the dog was able to maintain good motility and survived up to 11 years (the normal lifespan of a Golden Retriever), far exceeding the 1-2 year lifespan of the average GRMD dog. And one offspring of this Golden Retriever dog, inherited the same traits, suggesting that the improvement was not an accident, but the result of a transmittable genetic variation. So the researchers did a full comparison of the genomes of these two special dogs with those of other typical GRMD dogs (details not listed) and found that the two groups of dogs differed in the expression of a gene called Jagged1. Jagged1 gene expression was significantly higher in dogs with very mild disease than in dogs with severe disease, i.e., high expression of the Jagged1 gene significantly improved the clinical manifestations of DMD. It would be premature to draw conclusions from the GRMD dog study alone. So, another group of researchers conducted a study using a zebrafish model of DMD and artificially introduced the Jagged1 gene at the fertilized egg stage to enhance its expression. It was found that the treated zebrafish were significantly more active and had better muscle morphology than the untreated zebrafish. This cross-species study provides a good confirmation of the effect of enhanced Jagged1 gene expression on the alleviation of clinical symptoms of DMD. For the mechanism of action of Jagged1 gene overexpression to improve the clinical phenotype of DMD, it is believed to be related to the Jagged1/Notch signaling pathway, which is a ligand for Notch transmembrane protein, and this pathway is closely related to the repair after muscle injury. However, previous studies have shown that supplementation with exogenous Jagged1 does not enhance the Notch signaling pathway, but rather diminishes its effects. (Xiao, Y., Gong, D., and Wang, W. (2013). Soluble JAGGED1 inhibits pulmonary hypertension by attenuating notch signaling. Arterioscler. Thromb. Vasc. Biol. 33, 2733C2739). Therefore, the only way to treat DMD is to enhance endogenous Jagged1 gene expression through other small molecule drugs or gene therapy. We are very pleased to see that innovative therapeutic strategies and approaches continue to emerge for DMD, which is a current hotspot for gene therapy research, and also to shed more light on this disease. But on the other hand, there is still a long way to go before a possible therapeutic mechanism can be applied to the clinic. Many initially promising therapeutic strategies have previously been seen to be rejected and buried in subsequent studies. We can hold a cautious optimism, but the door to gene therapy will certainly open, no matter how many storms we go through.