Peter Pan: Breakthrough of Duchenne Muscular Dystrophy

INTRODUCTION:

Duchenne muscular dystrophy (DMD)is one of the nine types of muscular dystrophy. It is passed down through family genes and is considered a genetic disorder. It is characterized by progressive muscle degeneration and weakness. Individuals who suffer from this genetic disorder lack dystrophin which is a protein that helps keep muscle cells intact.(B)

BACKGROUND INFORMATION:

Symptoms of DMD can be seen in an individual's early childhood between the ages of 3 and 5 years old. Even though, this disease primarily affects boys, there are rare cases in which girls are affected as well. At the age of 3, muscle weakness can be in hip muscles, the pelvic area, thighs including the shoulders. The skeletal (aka voluntary) muscles in arms, legs, and trunk are affected later on. Another sign of a symptom are enlarged calves. By early teenage years, heart and respiratory muscles are now affected also. (B)

French neurologist, Guillaume Benjamin Amand Duchenne, first described what DMD was in the 1860s.There was very little known about this disease until the 1986 where MDA-supported researchers found a particular gene on the X chromosome that when mutated in some form or another leads to DMD. The protein associated with this gene was found in 1987 as 'dystrophin'. Without or lack there of this protein muscle cells become fragile and are easily damaged. This disease is genetically passed down through an X-linked recessive inheritance pattern which is passed down by the mother (i.e: the carrier). (B)

These females who are DMD carriers have a normal dystrophin gene on one X-chromosome and an abnormal dystrophin gene on the other X-chromosome. Carriers do not themselves have symptoms of the disease although a minority do experience signs and are affected. Mild skeletal muscle weakness to cardiac involvement to severe weakness or cardiac effects beginning in childhood or adulthood are just some of the wide range of DMD symptoms.(B)

Boys diagnosed with DMD typically do no survive beyond their teen years- until now. Thanks to advances in medicine such as cardiac and respiratory care, the life expectancy has been increasing allowing for these individuals having the possibility of living a full life of going to college, getting careers, and themselves having children and marrying. Males with DMD reaching their 30s are nowadays much more common and even some who live into their 40s and 50s. Research on DMD is still continuing as MDA-supported researchers pursue research in gene therapy, exon skipping, stop codon read-through and gene repair.(B)

RESEARCH:

Recent research suggests a breakthrough for DMD.  Researchers were able to slow the progression of DMD in adult mice using recently developed techniques that have been developed in 2015. Gene- editing injects could one day give hope to those with inherited DMD.Three teams of US researchers showed how gene editing tool could be used to 'correct' mutations in an animals muscle DNA which prevented the production of the protein dystrophin. These series of studies lead to partial recovery of the animals tested. (A)

DMD affect ~70,000 individuals who are living in the UK, making this genetic disorder to be one of the most common and severe diseases. Primarily seen in early childhood in boys, they become more and more immoble as they age to their 20s or 30s. DMD causes muscle degeneration, disability, and ultimately premature death. Unfortunately, DMD is incurable. New research suggests that gene-editing will soon be able to treat those with DMD through the deletion of a small piece of scrambled DNA which is the area that prevents the gene from working normally. So there is still much hope in this incurable genetic disorder.(A)

The mice that were treated in the series of studies were not completely cured because the dystrophin gene activity was restored to a state that it would be expected to achieve adequate muscle function in a patient with DMD. The gene-editing tool, CRISPR-Cas9, is able to cut out a tiny piece of flawed DNA with surgical precision while avoiding complex and difficult traditional gene therapy. It can be applied to adults. It also does not need any controversial tampering with genes in eggs and sperm that are then passed on to future generations.(A)

The way in which this gene editing tool works is that it  harnesses a defense mechanism that is used against viruses to focus on specific targeted sections of DNA. An enzyme that acts like a molecular 'scissor' then cuts the section away. This process has been shown to work on human cells just about 3 years ago. Other recent research studies, used a harmless virus injected to deliver the gene-editing components directly into the muscles of mice with DMD. This resulted in a small section of defective protein-coding DNA being “edited out”. Natural repair mechanisms then stitched the two loose ends of the DNA molecule together to create a shortened but working version of the gene.(A)

Study performed by scientists at Duke Univ. discovered a treatment that restored dystrophin protein levels to 8% which is the normal level for non DMD individuals. Previous research have shown that even at a 4% levels of dystrophin protein are enough to have adequet muscle function. the treatment restored dystrophin protein to roughly 8% of its normal level. In using CRISPR to correct genetic mutations in the affected tissues of sick patients show through the studies and their results a possible path that can be followed. Much more research is of course needed because authors of 'Writing in Science' say that such an approach could cause neuromuscular disorders and other diseases.neuromuscular disorders and many other diseases. (A)

Scientists at Harvard Univ. led a second study where they used a red fluorescent marker to show how the gene-editing treatment altered the development of muscle fibers. A third study was conducted from the Univ. of Texas which demonstrated that the treatment worked best when the gene-editing kit was injected directly into muscles. Before clinical trials can involve any human participants, researchers and scientists alike have to find any unintended consequences or side effects of these type of treatments.(A)

Links:
(A)http://www.theguardian.com/science/2015/dec/31/breakthrough-offers-hope-to-those-with-duchenne-muscular-dystrophy
(B)https://www.mda.org/disease/duchenne-muscular-dystrophy

*Please note! These images are not mine. They were found on various tumblr sites! If any are yours please let me know so that I can give you credit for them! Also the people in the images have no relation to the diseases, illnesses, or cancers I write about. Thanks so much & enjoy~