A Study On Duchenne Muscular Dystrophy

Duchenne muscular dystrophy was first discovered by Guillaume Benjamin Amand Duchenne in the 1860’s, but due to lack of medical knowledge little was known until the 1980’s. It was in 1986 that researchers that were supported by the MDA, muscular dystrophy association, identified the particular X-chromosome that leads to DMD, Duchenne muscular dystrophy. Dystrophin is the protein that is associated with the gene and was named in 1987.The DMD gene is the second largest gene to date, and it produces dystrophin.(Genome, 2013) Lack of the protein Dystrophin in the muscle cells causes them to weaken and become fragile. (MDA, 2015). DMD is an inherited disorder, but there are rare cases where it can spontaneously appear in a child with no previous family history due to a random mutation in moms X-chromosome. DMD is a gender specific disease that only appears in males.

Attention Getter: Nowadays, with the development of the technology in the medical industry, human health condition is getting better. There are so many different medicine, vitamin are used for improving the human immunes systems to fight against diseases. But there are still some dangerous disease that can not be cured yet and Muscular Dystrophy Disease is one of them.

Duchenne muscular Dystrophy (DMD) is the most common out of nine types of muscular dystrophy. This genetic disorder causes progressive muscular weakness, and deterioration due to the lack of a protein called Dystrophin. This protein keeps the muscles in tack, so when it's missing, the muscles slowly break down. (MDA, 2015)

Duchenne Muscular Dystrophy (also referred to as DMD) is a type of muscular dystrophy that weakens the muscles that we need to support our body, body weight, to stand, and to move around. It also can cause you to have scoliosis. Some of the main causes for DMD are genetic disorders, mutations, and DMD has to be passed down throughout everyone in that family for generations. The symptoms you can have if you have DMD are weak muscles, lack of strength, and difficulty walking. DMD is a negative mutation because it affects your muscles horribly bad that you can get a disability of walking and even moving. You need to tell your doctor immediately if you experience any symptoms. If you don't tell your doctor, you may find yourself in a very difficult situation where you can't get up or can't get something you need. When you do talk to your doctor, you will have an advantage of getting the help you need.

muscular dystrophy has many forms and therefore symptoms can vary between the variations. Overall symptoms include the weakening of skeletal muscles and the defect and death muscle tissues. Duchenne muscular dystrophy is the most common and affects young boys such as Eddie.

Muscular dystrophy (MD) is a rare, progressive disease relating to the weakening of skeletal muscles. There are more than 30 types of muscular dystrophy that are further divided into nine categories. Duchenne MD is the most common and acute form of this condition that accounts for 50% of all the cases. Duchenne MD (DMD) is most prevalent in males, between the ages of 3 and 5 (Norwood, FL, et al. 2009). This X-linked disease occurs for 1 in every 3,500 males, which results in confinement to a wheelchair (Blake et al., 2002). Becker MD (BMD) is a less severe type of this condition. A study conducted in the United Kingdom by Bushby, Thambyayah and Gardner-Medwin, the incidence of Becker MD was estimated to be 1 in 18,450 males at birth

DMD is caused by a mutation in the X-linked dystrophin gene, which results in a dysfunctional dystrophin protein. Dystrophin is a cytoskeletal protein that provides mechanical stability to muscle cells by connecting the muscle sarcolemma to the basal lamina of the extracellular matrix (ECM), and without it there, the muscle cells typically undergo a process of degeneration and regeneration. This process is limited by the survival of satellite cells present since satellite cells can only undergo mitosis a limited amount of times. Sarcolemma instability typically results in excess intracellular amounts of both sodium and calcium, which causes ATP depletion and mitochondrial uncoupling (Horn & Schleip, 2012). Satellite cells only have a limited number times they can undergo mitosis, and once a patient can no longer generate healthy muscle cells, the patient will typically experience cell death. This cell death and necrosis usually

Duchenne muscular dystrophy (DMD) is one of many types of muscular dystrophy disorders, which affect the muscle fibers. It is the most aggressive form of muscular dystrophy. The muscle fibers gradually become weaker and incapacitate the affected individual. “DMD is a recessive, fatal, X-linked disorder occurring at a frequency of about 1 in 3,500 new-born males (NCBI, 2014).” Males are more susceptible to inherit this disorder because DMD is passed on through the X chromosome. Women can be carriers of the disorder without any adverse affects. The female carrier has a 50% chance of passing on this trait to an offspring. It is extremely rare that a female will have DMD. Symptoms of this disorder include muscle weakness that starts at the legs and progresses at a fast rate though out the body. The rapid progression of muscular dystrophy means that the inflicted individual will eventually be confined to a wheelchair in their life time. “Wheelchair dependency had a median age of 10 years (OMIM, 2013).” Other symptoms include degraded motor skills as well as learning disabilities. As muscle mass diminishes the individual suffers from heart and lung complications eventually leading to the persons’ death. “Death occurred at a median age of 17 years (OMIM, 2013).” The X-linked inherited disease is cased by a mutation in the DNA segment of the X chromosome in the DMD (P11532) gene. This

Duchenne Muscular Dystrophy is one of the nine types of muscular dystrophy and the most known, it’s a genetic disorder distinguish by ongoing muscle degeneration and weakness. DMD is cause by a mutation on the X chromosome that stops the production of dystrophin, which is a normal protein in muscles.

Some of these strategies are promising and capable of restoring some motor function in spinal muscular atrophy models, especially increasing SMN protein production via upregulation of the SMN2 gene. However, this is a more global approach and these drugs have been shown to cause toxic side effects in other cells. Another more specific approach involves antisense oligonucleotide (AON) technology to modulate mRNA splicing in order to create additional functional SMN protein from the SMN2 gene as compared to the typical 10-30%. This has been shown to be effective in mice but the issue is the need for an efficient delivery system in humans. Another promising treatment strategy reprograms fibroblasts into induced pluripotent stem cells to compensate for the damaged motor neurons. This has been promising in the mouse model and may translate better to human motor neurons than other tactics. Some difficulties in developing effective treatments include unwanted toxic side effects and manipulating pharmacokinetics to allow for effective treatment. Scientists are working to develop a better understanding of the genetic mechanism of the disease and develop more efficient strategies of delivering drugs4. In addition,

Becker muscular dystrophy (BMD) is an x-linked recessive inherited disorder characterized by slowly progressive muscle weakness of legs and pelvis. This disease primarily effects voluntary muscles such as muscles of the hips, pelvic area, thighs and shoulders. Since this disease effects all your muscles they’d weaken your heart as well. Most people with BMD often develop cardiomyopathy ( disease in the heart muscle).

The editing of somatic cells, also known as gene therapy, is something that been used successfully several times already, while germline cell editing is a relatively new concept and not much research has been done. Genome-editing on somatic cells allows us to edit genes for the individual that are causing disease. Most diseases are found in the somatic cells and not in the germline cells. Somatic cell editing can be used to treat such diseases like Duchenne’s muscular dystrophy. Duchenne’s muscular dystrophy is an X-linked recessive trait, the process of editing the somatic cell is done in vivo. The process is done by reconstituting a functional dystrophin in the disease by

Like dystrophin, utrophin contains N-terminal actin-binding domain and C-terminal dystroglycan-biding domain (Tinsley et al., 1992). The nucleic acids and amino acids of Utrophin respectively share 65% and 80% identity with dystrophin (Love et al., 1989). Utrophin expresses ubiquitously in many fetal and adult tissues, including liver, spleen, skeletal muscle and testis (Love et al., 1991). Utrophin localizes in the neuromuscular junction of adult skeletal muscles, whereas it relocalizes to the sarcolemma in regenerating muscle fibers (Amenta et al., 2011; Ohlendieck et al., 1991). Sarcolemmal recruitment and upregulation of utrophin in the skeletal muscle of the mdx, the most common animal model of DMD with a nonsense mutation in exon 23, imply the compensatory role of utrophin for the loss of dystrophin (Amenta et al., 2011; Banks et al., 2014; Bulfield et al.,

But many view these risks as subordinate to the potential of gene therapy to help reduce and eliminate the social burden of genetic disorders. The ability of gene therapy to affect such disorders,however, is restricted to those caused by recessive X-linked or autosomal mutations. The realm of efficacy for treatment includes individuals afflicted with common disorders such as haemophilia, color blindness, Duchenne muscular dystrophy, phenylketonuria (PKU), cystic fibrosis, sickle-cell anemia, and Tay-Sachs disease(226-7). The treatment of such disorders must be monitored so that the replacement gene, once inserted, will be expressed at the appropriate time and place, and in the correct quantity(229). Improvements on regulatory techniques are then necessary to enhance the effectiveness of gene therapy. Furthermore, the effectiveness of such techniques is exceeded by the vast majority of the population afflicted with genetic disorders caused by

Adeno-associated viral vectors are non-enveloped single stranded DNA viruses used in treating diseases of the central nervous system 3. AAV vectors have been widely used in clinical trials to deliver therapeutic genes to mutated ones, and are efficient and safe in vivo application3. However one major drawback is the limited packaging capacity for genes with larger sizes 3. Fortunately, this can be overcome with the treatment of the dystrophin gene (DMD), which encodes the cohesive protein dystrophin that supports the cytoskeleton of a cell3. There are two methods can be used with AAV vectors to decrease the duration of epilepsy: inducing somatostatin into AAV vectors and direct injection of glial targeting AAV vectors.