Muscular Dystrophy

Muscular dystrophies are a wide group of inherited disorders characterized by gradual weakness and wasting, or atrophy, of different body muscles. There are many types of muscle dystrophy, yet the most widely known type – and unfortunately the most severe – is Duchenne muscular dystrophy (DMD).

Symptoms of muscular dystrophy vary greatly depending on the type of defect – and therefore type of Muscular Dystrophy. For example, symptoms seen with DMD are more severe and rapidly progressing than those seen in milder forms such as Becker muscular dystrophy. The most common type of muscular dystrophy is DMD and it typically presents at around 4-5 years with (1, 2):

• Gradual muscle weakness and wasting
• Delay of reaching motor milestones
• Loss of previous ambulation (ex. Standing/walking)
• Recurrent respiratory complications (due to abnormal breathing muscles)
• Cardiac abnormalities (usually by the age of 20)

People with the more severe DMD form typically become wheelchair-ridden by the age of 12, and usually develop severe complications due to cardiac and respiratory complications – rather than due to direct muscular problems (1).

Given that muscular dystrophies occur due to inherited genetic defects in the genes responsible for proper muscle development and functioning, its treatment options are limited, similar to lots of other inherited disorders. Current treatment options for muscular dystrophies include:

• Physiotherapy: Physiotherapy is still the main form of therapy for muscular dystrophy – along with steroids (2).
• Steroids: Steroids are strong anti-inflammatory drugs that can also modulate the body’s immune response. There is current evidence that early use of glucocorticoids/steroids delays the onset of wheelchair dependence. However, to this day and despite extensive studies on the topic, there are still uncertainties regarding which steroid is the best to use and the possible risk of under or over-treatment. This is also in addition to the potential side effects of prolonged steroid use such as weight gain and higher risk of infections (2).
• Gene Therapy: this is yet again another promising mode of therapy – similar to stem cell therapy – with multiple drugs being approved by the FDA for muscular dystrophies due to the limited amount of options available. These drugs target the gene abnormality responsible for muscular destruction and dystrophy; however given that these medications target a certain genetic mutation, they depend on a certain genetic mutation/aberration being present in the patient in order to be able to use it. For example, one drug approved known as Eteplirsen has been reported to be efficacious only in around 15% of patients with DMD who carry a certain mutation in Exon 15 of the DMD gene. This means that in children who have a gene abnormality elsewhere or even a different abnormality within the same gene – which is common – don’t benefit from this medication. Therefore, gene therapy requires a meticulous genetic assessment before its use (3, 4).

To date, there has not been a single study – to our knowledge – that has compared different types of stem cells, concerning safety and efficacy, particularly in patients with muscular dystrophies. However, we can summarize different stem cell sources that have been tested in these disorders. Each form of stem cells has its own benefits and drawbacks as will be mentioned. Different stem cell sources that have been tested in different muscle dystrophies – either on animals or in humans – include (5, 10):

• Mesenchymal Stem Cells: These are stem cells obtained from adipose tissues, bone marrow, or umbilical cord tissues – which we actually use at Beike. These cells are the most widely used stem cells since they can be easily produced in larger numbers to accommodate a higher number of patients and allow better efficacy, have a better response in neurological and muscular diseases, have better differentiation capacity into numerous cell types, and have better anti-cell death effect in case of degenerative conditions like muscular dystrophies that cause progressive muscle wasting – compared to other stem cells. Mesenchymal stem cells can be obtained from different sources including the umbilical cord, bone marrow, and adipose tissue.
• Muscle/Satellite Stem Cells: These are another type that has particular benefits in differentiating into the defective muscle fiber cells, of the same origin; though their use is limited in patients due to their limited migration abilities to the site of defect following their transplantation. These stem cells also require long-term suppression of immunity using immunosuppressants to prevent transplant rejection.
• Adult Pluripotent Stem Cells: These are another source that can be produced in large numbers, yet their differentiation abilities are limited.
• Embryonic Stem Cells: Another type of stem cell includes embryonic stem cells. These cells can also differentiate into photoreceptors, yet they are difficult to obtain and have ethical concerns regarding their sources.

After carefully reviewing all of the benefits and risks of each type, we have decided to use mesenchymal umbilical cord-based stem cells as our main source since they have been the most extensively studied type in neuromuscular conditions, including muscular dystrophy, with the least reported side effects (6). This is in addition to also using umbilical cord blood cells (hematopoietic cells) concurrently to provide additional benefits from using two types of stem cells; with each contributing to muscle and nerve regeneration through different complementary mechanisms.

In addition to the source of stem cells, there are also multiple routes of stem cell administration. Most clinical trials testing stem cell therapy in Muscular Dystrophy use either one – or both – of preferably two routes; which are (10):

• Intravenous (Into the blood)
• Intramuscular (Locally into the muscles)

Studies have shown that in contrast to a single route of intravenous administration, administering stem cells through dual administration provides significant clinical results and improvement (10). At Beike, we use combined intravenous and intramuscular routes concomitantly to achieve the best results with the least possible side effects.

At Beike, we use umbilical cord stem cells for muscle dystrophies, both umbilical cord-related mesenchymal/tissue and blood/hematopoietic cell samples donated from healthy mothers after a normal birth. As previously mentioned, this concomitant administration of both types of stem cells, mesenchymal and hematopoietic stem cells, provides better results.

There is no specific timing for stem cell treatment, but like many other neurological conditions, we generally recommend seeking stem cell therapy early after diagnosis – i.e. during childhood. This is because the earlier the stem cell intervention, the easier it is to prevent further damage to the muscle fibers and to be able to restore normal mobile functioning before permanent damage and muscle atrophy/wasting take place.

We still need to report that clinical benefit is not 100% guaranteed as is the case with any intervention, and consulting our specialists prior to undergoing the procedure is of utmost importance in order to gain more insight into the procedure and the estimated possibility of treatment success for your individual case.

Of course, no treatment is without complications, and stem cell therapy is the same. However, despite its novelty, mesenchymal stem cell therapy has limited side effects, if used properly, with comparable general side effects to those experienced with regular blood transfusion or foreign organ transplantation (ex. allergic reactions, cell rejection, or fever). Additionally, in studies specifically studying stem cell therapy in patients with Muscular Dystrophy, no significant side effects were reported and none were life-threatening or had life-long consequences when mesenchymal stem cells were used (10). They were also easily managed medically at the time of their occurrence.