Running Head: DUCHENNE MUSCULAR

Treatment of Duchenne Muscular Dystrophy by Myoblast Transplantation Rachel Stagg Chesapeake College Bio 211

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Treatment of Duchenne Muscular Dystrophy by Myoblast Transplantation

Duchenne Muscular Dystrophy (DMD) is a severe, recessive X-linked muscular dystrophy characterized by progressive muscle degeneration; it affects about one in 3,500 male births (Palmieri, Tremblay & Daniele, 2010 para. 1). The distinguishing progressive muscle weakness starts around five years of age. By 10-12 years, the child is likely confined to a wheelchair, and most patients die from respiratory complications between the ages of 17 and 30 (Palmieri, Tremblay & Daniele, 2010). DMD is caused by genetic defects on the gene that arranges for Dystrophin (Palmieri, Tremblay & Daniele, 2010). Mutations of dystrophin cause cellular mutilations, and delicacy and vulnerability of muscle fibers of many muscular organs during contraction (Palmieri, Tremblay & Daniele, 2010). The continuous lack of dystrophin (it only deteriorates further with increasing age) makes muscle remain vulnerable throughout contractions, which trigger continuous damage-repair cycles (Palmieri, Tremblay & Daniele, 2010 para. 2). This leads to rapid myoblast (type of cell with forms myocytes, or muscle fibers) aging and degeneration (Palmieri, Tremblay & Daniele, 2010). The life expectancy for patients with Duchenne muscular dystrophy is so low because damaged muscles are progressively replaced by fat and connective tissue in the later stages of the disease, rendering them essentially useless (Palmieri, Tremblay & Daniele, 2010 para. 2). There have been many different attempts to slow the muscle degeneration process in the past; but, most of these have not been successful. Some of these experiments include early cellular therapies and even early myoblast transplantation treatments. This article discusses a new clinical aim to transplant myoblasts into a small muscle of the forearm, and hopes to allow greater independence in patients with DMD (Palmieri, Tremblay & Daniele, 2010).

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In the past there have been several varying types of myoblast transplants experimented with on mice, dogs, primates, and even a few humans. The techniques did not work previously for many reasons: inadequate immunosuppression, subtle changes of the myoblasts before retransplantation, and the unavailability of a sufficient amount of muscle strips to transplant (Palmieri, Tremblay & Daniele, 2010). Later, after success, this research group began research with Myoblast Transplantation (MT) in monkeys, because the immune system and size of their bicep muscle is comparable to that of a human (Palmieri, Tremblay & Daniele, 2010). This experiment proved fairly successful; 75% of fibers were of hybrid origin after one month in the bicep of the monkeys, and they stayed present for over a year after MT. Currently, many scientists and researchers are trying to use stem cells, rather than transplanting a whole organ, because it creates fewer complications than solid organ transplantation (Palmieri, Tremblay & Daniele, 2010). In a new clinical trial, also done by Palmieri, Tremblay and Daniele, myoblasts were transplanted into the extensor carpi radials and combined with six months of immunosuppression. The patients of the study were all under the age of 18 years, because past 18 years the patient is considered to be in a very advanced stage of the disease, with many of their muscles replaced by adipose or scar tissue. The researchers assumed that if muscular function, observed at a follow-up appointment, was conserved or enhanced, then myoblast transplantation into other muscle groups was wise to prevent further degeneration (Palmieri, Tremblay & Daniele, 2010). It is the hope of this research group that this method can improve muscle strength and promote autonomy in patients with DMD. So far, myoblast transplants have been fairly successful in animals, and somewhat successful in humans. As this article says, we are living in the stem cell age (Palmieri, Tremblay & Daniele, 2010 para. 32). Research and procedures with stem cells right now are

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promising, and in regards to skeletal muscle diseases, the concept of repairing defective muscle fibers is possible (Palmieri, Tremblay & Daniele, 2010 para. 32). The research group fully believes that MT benefits will last a lifetime, because there is evidence that transplanted myoblasts have transformed to a type of satellite cell that was able to repair the spoiled muscle fibers (Palmieri, Tremblay & Daniele, 2010 para. 33). In mice that received the beneficial effects of MT and were subjected to monthly exercise, damage was only observed in the dystrophinnegative fibers, not the dystrophin-positive fibers. It was concluded that myoblast transplantation protected the muscle tissue of the mice from mechanical stress on muscles which triggers muscle fiber death, which means muscle fibers in patients with DMD may be able to have the same results (Palmieri, Tremblay & Daniele, 2010). This method will hopefully transfer to humans very soon, so that males born with Duchenne Muscular Dystrophy can prolong their life and hope to be somewhat self-reliant. In humans, myoblast transplantation should be implemented as soon as muscle failure signs appear because a lower number of cells would be required and the quality and amount of viable muscle fibers will be higher. It is a constant struggle and learning experience to make MT a simple, safe and effective procedure (Palmieri, Tremblay & Daniele, 2010). Since we are indeed living in the stem cell age, further experimentation with stem cells can be conducted to further the research in prolonging the life of patients with Duchenne Muscular Dystrophy. This horrible, debilitating disease is typically fatal by the late teenage to early adulthood years. That is tragic, and if more experimentation is done with stem cells, researchers will know how successful myoblast transplants may become in the future. There has been success with monkeys in at least one large muscle, the bicep. Primates are very close to humans, so the results are more beneficial to humans than the research done with mice. Monkeys

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were found to have hybrid cells that were not degenerating in the bicep muscle after successful myoblast transplantation that stayed for over a year. I hope to see more research done with monkeys soon, because they are very closely related to our chemical makeup, and the more we know about success with monkeys, the more success we can have with humans. Also in the future, there is hope for better immunosuppressive drugs that may reduce the risk of graft vs. host disease, and make the transplantation process much easier, particularly after the transplant occurs. Graft vs. Host disease occurs when the grafted muscle (or organ) is not recognized by the body or thought to be a foreign object, and is fought off by the body. This would be a dreadful occurrence for someone with muscular dystrophy who is hoping to have healthy muscle fibers implanted into their body to regenerate. This research group also mentioned the hope of successful myoblast transplants in a small muscle, such as the extensor carpi radials, leading to increased myoblast transplant in the same patient to reduce further muscle atrophy (Palmieri, Tremblay & Daniele, 2010). However, it doesnt appear this specific experiment was conducted yet, and this is an area that should be expanded upon to know if autonomy and increased muscle strength in one patient is possible. I think that very soon in the future, because of increasing knowledge of medical practices and procedures, DMD patients can be accurately assisted or treated with myoblast transplantation.

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References Palmieri, B., Tremblay, J. P., & Daniele, L. (2010). Past, present and future of myoblast transplantation in the treatment of Duchenne muscular dystrophy. Pediatric Transplantation.