Muscular Dystrophy: Types and Designed Proteins for Treatment

Proteins, which sum up to 42% of the total dry weight in our body, play an important role as part of the red blood cells and as collagen. This is mainly responsible for holding our body parts together. Moreover, proteins also work together to activate an enzyme and turn on a gene. Muscles, on the other hand, are mainly used for body movements, digestion of food, excretion of body waste, heart function, and all activities happening inside the body. Without muscles, it is definitely impossible for the organs in the body to normally function and the body to move in any direction. Normally, our body produces enough proteins for fit and healthy muscles. However, in the case of those with muscular dystrophy, there is an obvious progression of weakness (decreasing of muscle size) and muscle wasting due to the mutations of genes that are mainly responsible for the production of proteins for utilization.

Muscular dystrophy manifests a variation of signs of symptoms, depending on the type of muscular dystrophy. Most of the types affect males in their childhood years, yet some do not appear until adulthood and can appear on either male or female individuals. Since it is a genetic disorder, it cannot be transmitted through blood transfusions, direct or indirect body contact, accidental needle pricks, and all other possible ways of acquiring infections.

Duchenne and Becker Muscular Dystrophy: Their Protein Mutations

There are several types of muscular dystrophy and Duchenne Muscular Dystrophy is the most common type. This type of dystrophy is caused by an absence of dystrophin protein and appears in early childhood. It commonly affects the male population, albeit in rare cases, females are affected with this disorder. Females are more commonly known to be the carrier of this genetic defect. The symptom appears in the legs first and patients may develop scoliosis. Other symptoms may include difficulty in breathing, difficulty in learning, heart and lung problems, and contractures.

Another type of dystrophy, a variant of Duchenne Muscular Dystrophy, is Becker Muscular Dystrophy. This type of dystrophy is caused by a shortened form of dystrophin, a cytoplasmic protein which is of rod-like shape. It mainly affects voluntary muscles, though the muscles affected can be more functional than those with DMD. Unlike DMD that onsets in early childhood, BMD usually affects individuals in their late childhood or the adolescent stage. (Reference: Mda.org)

Other Muscular Dystrophy Types 

1. Congenital: Muscle weakness is observed in newborns and infants, and there are possible joint deformities. In rare cases, this type can cause intellectual disabilities. Newborns and infants with this disorder are expected to have a short lifespan. Infants with this condition are labeled as “floppy infants.”

2. Distal: It is usually observed in individuals in his or her 40's to 60's. Symptoms include weakness and waste of muscles of those parts farther than the shoulders and hips – the hands, forearms, and lower legs in a slower progress. Other individuals with this type of disorder may have difficulties in speaking and swallowing and may experience heart problems.

3. Emery-Dreifuss: It is commonly observed in childhood to early adolescence. The symptoms of the said type can be observed in the shoulder, upper arm, and skin muscles (mostly skeletal muscles – muscles used for movements). Joint deformities are also common. Progression may be slow but can be fatal if cardiac problems occur.

4. Facioscapulohumeral: It is another type that can affect both boys and girls and usually begins in childhood to early adults. The symptoms are observed on the face, shoulders, and upper arms. In some cases, lower legs are also affected. Whistling, tightly closing the eyes and arm raising might be difficult for individuals with this type of disorder.

5. Limb-Girdle: It affects both genders and affects the shoulders, upper arms, and around the hips and thighs. It can be observed in individuals in their late childhood or their middle age. As the disorder progresses, those affected by this type might be needing a wheelchair over time or worst, die due to cardiopulmonary complications.

6. Myotonic: Another type that usually affects individuals in their 20's to 40's. Symptoms include weakening of all muscle groups. An individual with this type of disorder can experience difficulty in relaxing. Teens can also be affected and exhibit a number of problems including cataracts and cardiac problems. Lastly, the progression is rather slow.

7. Oculopharyngeal: Individuals with this type of disorder are usually in their 40's to 70's. The symptoms affect the muscles of eyelids and throat. Over time, people with this type of MD experience inability to swallow and becomes weak since they can no longer eat food.

Designed Proteins as Muscular Dystrophy Treatment

Life expectancy varies on the type of muscular dystrophy and how rapid or slow the disorder progresses. There is no cure for this genetic disorder or treatments to stop the progression of the disorder fully. However, medications and therapies are given to patients with muscular dystrophy to slower the progression of the symptoms. Some types, if left unattended, may start affecting the heart and lungs, leading to death. A study about congenital muscular dystrophy has been conducted by the research group of Professor Markus Rüegg at the University of Basel. Through the use of mice as their experimental subject, they were able to identify and demonstrate two proteins that can restore muscle force, increase body weight, and most significantly, prolong lifespan.

One protein mentioned in their research is laminin α2. Laminin α2 is mainly the component for cell scaffolding and connecting the inner part of the muscle fiber. A defect of this protein can make the muscles dysfunctional, subsequently, causing inflammation and degradation of muscle fibers. The mutation of this protein is mainly responsible for 30% of congenital muscular dystrophy cases. The researchers were able to observe that in the absence of this protein, another protein called laminin α4 replaces the role of laminin α2, though not as effective as the first protein.

The researchers were able to pull off an idea by creating two new proteins to help laminin α4 fully anchor to the muscle cell. When mice with a defective laminin α2 protein were able to express those two linkers, there were significant improvements in the muscle structures and force. Furthermore, almost normal lifespan was observed.

They were also able to observe similar structural defects and laminin α4 in place of laminin α2 through a biopsy of individuals with congenital muscular dystrophy. Professor Rüegg said that there is a possibility for the designed linker proteins to treat congenital muscular dystrophy through gene therapy. The study conducted by the University of Basel is an excellent example which proves that molecular and cellular understanding of the disease can help develop therapeutic options. The researchers are now interested in exploring the possibility of using linker protein to improve muscle function.

Though medical professionals are still holding this research for the further study, it has not been crushed out of the list of treatment to be used in the future. Hopefully, in time, it will be proven as one of the most effective ways in treating congenital muscular dystrophy and could be the start of finding another effective treatment for the other types of muscular dystrophy.