A New Advancement in Treating Duchenne Muscular Dystrophy

Introduction

Duchenne muscular dystrophy, also known as DMD, is a severe inheritable genetic condition without a cure, which becomes evident in young males, aged 1 to 6. This disorder results from a frame-shifting mutation in the DMD gene, the third largest gene in the body, which is responsible for a muscle protein named Dystrophin. This complex protein is vital to the function, structure and protection of muscles and muscle fibres. Mutation of this gene causes damage to the skeletal and cardiac muscles as they contract and relax repeatedly. As this damage continues muscles cells weaken and die, wasting the muscle away and provoking heart problems at a very young age.

DMD is evident in approximately 1 in every 3,500 boys of early childhood driving scientists, doctors and pharmaceutical companies around the world to collaborate and develop a life changing cure for these boys. With the help of financial aid and sharing of relevant data with international conventions, recommendations, innovative technology as well as relevant research, companies and doctors such as ‘Sarepta’, ‘Solid Biosciences’ and Dr. Jerry Mendell have been able to conduct three individual trials using gene therapy. In each trial forms of micro-dystrophin were administered to patients by means of vector carriers, showing signs of hope for finding the cure for Duchenne muscular dystrophy. The SHE concept being explored in this report is ‘Communication and Collaboration’ and in particular the role this concept has played in the application of this revolutionary therapy technique.

The diagnosis of DMD is made through review of a patient’s weakness, delay of development, elevated serum creatine kinase (an enzyme released by damaged muscles), and confirmation via genetic testing and muscle biopsies. The current treatment of the disease through corticosteroids, bisphosphonate treatments and other medications aim to slow the onset of cardiomyopathy, prolong ambulation and prevent bone density loss. Exondys 51 is the only drug approved in both America and the United Kingdom to directly treat DMD as it is ‘designed to skip over the mutation in the DMD gene’ but only works for a small amount of people with a specific mutation. Due to advances in gene transfer technology, theories communicated by science communities around the world can finally be put into action as gene therapy has become a possibility for sufferers of Duchenne muscular dystrophy.

Gene therapy aims to treat genetic diseases via the correction of mutated genes at a molecular level in a clinical environment. This manipulation and replacement of the DMD gene is completed using an adeno-associated virus (AAV) carrying a micro or mini dystrophin. As dystrophin is the third largest gene in the body, at first seemed too large to be carried by a vector as it is three times the size of what can fit into the vector, but scientist Jeff Chamberlain developed a micro-dystrophin and mini-dystrophin design that has 17-48 exons left. The development and results of micro-dystrophin through the collaboration of scientists has allowed pharmaceutical companies internationally such as Solid Biosciences, Sarepta, Pfizer and doctors to undergo clinical testing enrolling patients for trialling of the new treatment.

In these trials Adeno-associated viruses were rid of their disease causing genes and replaced with micro-dystrophin to be injected into the patient’s arm. The virus then travels into the cell membrane and transfers the genetic information ready for protein synthesis of dystrophin.

Risks associated with this therapy include an undesirable immune system attack on the vectors, damage to healthy cells and greater infection caused by the vectors turning back to their original form. Sarepta Therapeutics’ clinical trial was conducted at Nationwide Children’s Hospital in Columbus by Dr. Jerry Mendell and in collaboration with non-profit organisation ‘Parent Project Muscular Project’, this trial received a $2.2 million dollar grant funding the process. This funding contributed towards the manufacturing of the vectors and costs for study participants that received the new treatment. In this trial twelve patients from the two cohorts of 3 months to 3 years of age and 4 to years of age, were given a dose of micro-dystrophin made for 60-70% of the DMD population. This study found that after 90 days there was an increased amount of micro-dystrophin in all patients’ muscles, a significant decrease in enzyme creatine kinase (CK) and there were no serious side effects.

All of the findings from this clinical trial displays a positive outlook on the developments of gene therapy as a cure for Duchenne Muscular therapy. These results were verified and reviewed by the Food and Drug Administration in the US and European Medicines Agency in the UK and after communication they are allowing further investigation into the treatment internationally. The use of gene therapy to treat Duchenne Muscular therapy has not only created hope for a cure for the genetic disease among global science communities but also has the potential to change the quality of life for young boys all around the worlds that are struggling every day to complete basic activities. Mendell and his team from Nationwide Children’s Hospital have recommended more trials of this treatment before it is viable to all DMD sufferers as the participants that took part in the test only had little muscular atrophy.

As soon as further investigations are completed and the treatment is approved by the FDA, EMA and TGA, communication between scientists, doctors and pharmaceutical companies internationally must take place for the implementation of gene therapy in clinical practices. For families with a child diagnosed with Duchenne muscular dystrophy, it may be distressing to see their child finding it difficult to stand up; walk, jump and run as their muscles weaken but also have a possibility of their heart muscles may fail. This loss of ability to walk takes place in years 7-13 and death is common in teens and early 20s. Any chance to see their child gain normal movement is extremely important as they may drop out of physical activities a young boy are part of such as team sports which is also important for social interactions.

It is fair to say that for the average family income, treatment of this kind is unachievable even as the treatment seems to be extremely beneficial for the patients. This was seen after the Sarepta and Mendell’s trial as in January at the start of the trial the boys could hardly walk up a flight of stairs, clasping on the handrail, but 90 days after the treatment they were able to easily run, ride scooters and climb up the stairs (Rabinowitz, 2018). Due to the trials collaboration with Parent Project Muscular Duchenne, these boys were able to receive a grant to take part in the study but for every other family in need of this treatment it seems unreachable. If gene therapy is approved for the treatment of DMD there must be some sort of funding to help the families that are unable to afford the cost of the therapy but their child drastically needs it. Communication and collaboration of governments, pharmaceutical companies and doctors will be required to make this treatment possible in the near future for the young boys who need to treatment desperately.

Conclusion

Duchenne Muscular Dystrophy has a vast impact on young boys internationally affecting their quality of life and ability to take part in everyday activities like walking and standing up but with new advances in gene therapy treatment technology, this disease may become non-existent (BioNews Services, n.d.). Communication and Collaboration has had a major role in these advancements through the review of data and findings, funding of trials, expression of possible theories as well as the approval of trials from government food and drug agencies. It is evident that gene therapy treatment of DMD shows a positive prospect for the future and it will have a substantial impact on the health and wellbeing of young boys diagnosed with DMD as well as their families, but more trials must be conducted to ensure there are no side effects or negative long term effects.