## 2 Therapeutic Approaches
### Anti-Inflammatory and Antioxidant Treatment  
There has been various histological evidence that the markers of inflammation and oxidative damage are increased in the muscles of FSHD patients through the muscle biopsy of FSHD patients [30; 31; 32; 33], and the level of proinflammatory factors such as TNF\(\alpha\) is detected in the muscles of FSHD patients, which is related to the spontaneous contraction ability of skeletal muscle [14]. Oxidative stress is one of the characteristics of various muscular diseases such as DMD, myotonic dystrophy (DM1), and limb girdle muscular dystrophies (LGMD) [34; 35; 36]. In vitro studies [37; 38] have shown that FSHD myoblasts are usually able to repair moderate oxidative damage under normal conditions, but they are unable to complete it when the level of oxidative stress is too high. In addition, two prominent extramuscular features of FSHD (retinal telangiectasia and sensorineural hearing loss) are also closely related to oxidative stress [39; 40]. Therefore, targeting the pathological damage in patients' muscles by reducing inflammation and oxidative stress is one of the effective treatment strategies.  
Glucocorticoid is a kind of corticosteroid that has strong anti-inflammatory properties. It was first discovered in the blood of patients with [PERSON]'s disease in 1949, and high levels of cortisol have been found to alleviate inflammation in patients with arthritis [41]. Clinical trials have been conducted to evaluate the effects of prednisolone in FSHD patients [42; 43; 44]; muscle biopsies indicate that after the intervention, patients either experienced a worsening of their condition following initial improvement or showed no significant changes, the study was inconclusive and there was a large amount of variability between individuals. Considering the side effects of long-term use of glucocorticoids, including osteoporosis, immunosuppression, and adrenal atrophy, this strategy cannot be used as a viable long-term solution.  
Conventional antioxidant therapy can alleviate pathological levels in FSHD patients both in vitro [45; 46; 47] and in vivo [48; 49], although with modest efficiency. Studies have utilized three different antioxidant compounds--vitamin C, coenzyme Q10, and mitoTEMPO--to treat the myotubes of FSHD patients, detecting the levels of reactive oxygen species (ROS) before and after the intervention [48]. The results suggested that all three compounds reduce the ROS level of myotubes with similar efficiency, which proves that the pathological mechanism of redox directly targeting FSHD can have a direct and beneficial impact on myogenesis of patients, although this mechanism is not clear. In addition, nutritional supplements such as vitamin E, zinc gluconate, and selenomethionine can enhance the antioxidant defense of FSHD patients, which can significantly improve the maximum voluntary contraction ability and endurance of bilateral quadriceps.  
Since DUX4 gene was identified as the pathogenic gene of FSHD, the therapeutic strategy of FSHD is changing to targeted therapy [50]. More studies have targeted DUX4 to treat FSHD. FSHD is caused by the abnormal expression of DUX4, so effectively inhibiting the expression of DUX4 may cure FSHD. Based on the pathological mechanism of FSHD, both upstream and downstream of the DUX4 are considered potential therapeutic targets. We sort out the latest targeted therapies as follows.