The research on effective DMD treatments Essay

Though ROS serve as critical second messengers in various cell signaling pathways, they are generally toxic to cells (Devasagayam et al. 2004). When the cell's antioxidant defense system cannot counteract an excess of free radicals, the buildup of free radicals in the body induces a phenomenon known as oxidative stress that can cause cell damage and/or cell death (Devasagayam et al. 2004). In muscle lacking dystrophin as in patients with DMD, mitochondrial function is impaired due to calcium overload in the mitochondria. This mitochondrial dysfunction permits an excess of harmful free radicals to form (Kelly-Worden and Thomas 2014). Consequently, the overload of free radicals in the mitochondria leads to cell damage and eventually cell death as apoptotic signaling pathways are activated in the mitochondria (Kelly-Worden and Thomas 2014). In addition to driving the initiation of apoptotic pathways and muscle tissue necrosis, ROS and free radicals can also prompt the formation of the MPTP (Kelly-Worden and Thomas 2014). Though researchers have not determined the exact cellular mechanisms underlying DMD, past research has determined that atrophying muscle is eventually replaced with fat and connective tissue.
To date, no effective treatments exist for DMD. Although current treatments for this disease such as corticosteroids, physical therapy, and respiratory interventions, slow the progression of symptoms and can help extend the lives of DMD sufferers, the disease is still lethal and survival beyond 30 years is a rare event (Fairclough, Wood, and Davies 2013). Thus, ongoing DMD research is pushing for the development of effective treatments. Gene therapy technologies are among the most promising treatments (Fairclough, Wood, and Davies 2013). Virus mediated gene therapy is one type of gene therapy researchers are looking into. This kind of gene therapy involves modifying viruses to deliver the functional dystrophin gene to DMD patients (Seto, Ramos, Muir, Chamberlain, and Davies 2012). The challenge of this therapy is discovering safe and effective ways of directly replacing the dystrophin gene in all the muscles of the body (Seto, Muir, Chamberlain, and Davies 2012). The CRISPR/Cas9 system is a recently discovered type of gene therapy that holds promise for the future of DMD. This genome editing technique involves manipulating bacteria's natural viral defense system and applying it to potentially edit human genomes ("CRISPR in the Lab"). In the case of DMD, the CRISPR-CAS9 system can be engineered to remove mutations in the dystrophin gene, allowing the DNA break to be repaired either through nonhomologous end joining or by homologous recombination with an undamaged donor DNA template (Long et al. 2014). The advantage of this therapy over viral mediated gene therapy is that the CRISPR-CAS9 system is potentially more accurate and able to permanently correct the DMD mutation (Long et al. 2014). Though scientists in 2014 successfully used the CRISPR-CAS9 system to treat mice that were genetically modified to have DMD, more testing in other animal models must take place and CRISPR's ethical issues must be addressed before this therapy will ever be deemed safe to use in humans (Long et al. 2014).