Stem cell therapy for Muscular Dystrophy
Muscular Dystrophy (MD) is a group muscle disorders causing weakness, and are classified into 9 types of muscular dystrophy . Muscular dystrophy symptoms lead to progressive muscle damage and deterioration and stem cell therapy for muscular dystrophy is emerging as a potential treatment option for Muscular Dystrophy.
Muscular dystrophy, as the name suggests, is a disease which leads to slow and ongoing damage of muscles of the patient’s body. The main muscular dystrophy cause is often attributed to be genetic. The common muscular dystrophy symptoms seen in patients include frequent falls, difficulty in getting up from lower surfaces/floor, difficulty in climbing stairs, problems while performing overhead activities in day-today life, difficulty in talking, breathing problems, poor stamina for performing even simple everyday activities and so on. There are 9 different types of muscular dystrophy each characterized a different set of muscles being affected. Inspite of the availability of advanced drugs and rehabilitation programs, there is no known cure for MD. Research being done all over the world has thrown light on stem cells and stem cell therapy for muscular dystrophy as a viable treatment option for the affected individuals with marked improvements in overall activities of daily living.
Muscular Dystrophy – An Overview
According to the Centre for Disease Control and Prevention, the global statistics for muscular dystrophy indicate that 1in 3500 live male birth are being diagnosed with Muscular Dystrophy. A recent study carried out by CDC, has thrown light on the fact that 90% cases of muscular dystrophy in the 19- 24 year age group succumb to the use of the wheel chair.
Muscular dystrophy is a condition in which muscles start getting weaker and weaker day by day with an increase in muscle weakness over time. The patient loses his ability to perform simple daily tasks like walking, climbing stairs, lifting objects, and eventually becomes wheelchair bound. These disorders are generally passed on from one generation to the next as they are known to have a genetic origin. But these disorders can also occur in families with no previous history of the condition.
The condition is further classified into 9 different types including Ducchene, Becker, Limb-girdle, congenital, facioscapulohumeral, myotonic, oculopharyngeal, distal and Emery- Dreifuss on the basis of the gene mutation, age of the onset, symptoms and so on.
Muscular Dystrophy Causes:-
The main cause of muscular dystrophy has often attributed to be the presence of an abnormal gene or defective gene.
Genes control the functions of each cell in our body including the muscle cells. These genes are also responsible for the production of certain proteins including Dystrophin protein that is responsible for the smooth functioning of the muscles.
When these genes are affected, the protein production is not regulated efficiently leading to muscle related disorders.
In Muscular Dystrophy, dystrophin protein required for the muscles is not produced properly. Either the protein is absent or present in very little quantity which leads to muscle damage and weakness.
Depending upon the faulty gene or faulty protein, the type of muscular dystrophy is distinguished.
Types of Muscular Dystrophy and Muscular Dystrophy symptoms:-
Muscular dystrophy is further classified into 9 different types including Ducchene, Becker, Limb-girdle, congenital, facioscapulohumeral, myotonic, oculopharyngeal, distal and Emery- Dreifuss on the basis of the gene mutation, age of the onset, symptoms and so on.
Duchenne Muscular Dystrophy (DMD) is the most common childhood form of MD mainly seen in boys. Classic features of DMD include muscle weakness of the legs, pelvis, neck, shoulder and arm along with a positive Gower’s sign. In some cases, the cardiac muscles are also affected.
Becker’s Muscular Dystrophy (BMD) is a less severe form of DMD with a slower rate of progression. Noticeable signs of BMD include lack of strength in the pectoral and upper arm muscles, legs, pelvis, arms and shoulders. The symptoms maybe unnoticeable in the early teens with the final diagnosis happening in their thirties.
Limb – girdle Muscular Dystrophy (LGMD) can be diagnosed either in early teens up to adulthood. As the name suggest, the patients’ exhibit weakness of the shoulder, face and upper arms. The rate of progression of the disease is slower as compares to DMD and is less severe.
Congenital Muscular Dystrophy (CMD) are a group of neuromuscular disorders with onset of symptoms since birth. Infants with CMD often exhibit muscle weakness and joint contractures either at birth or within the first few months of birth. Rigidity of the spine, muscle hypertrophy and problems in respiration are other noticeable features.
Emery – Dreifuss Muscular Dystrophy (EDMD) is a rare form of the disorder. The onset of the disorder is in early childhood and the progression is relatively slow. It is characterized by early contractures in the elbows, ankles and neck, progressive muscle wasting and weakness beginning in the upper arms, lower legs, shoulders and hips.
Oculopharyngeal (OPMD), Myotonic (DM) , Facioscapulohumeral (FSHD), Distal (DD) are some other common types of MS, which have their routes in childhood and the symptoms manifest themselves in early or late adulthood. (https://www.neurogen.in/muscular-dystrophy)
Stem Cells and Muscular Dystrophy
Inspite of the number of treatment options currently available for helping patients affected with Muscular Dystrophy, none focus on regenerating and repairing the damaged muscles. Stem cell therapy is one of the evolving treatments showing promising results for muscular dystrophy.
Autologous bone marrow derives cell transplantation, intrathecally and intramuscularly, is safe and an effective option for slowing down deterioration and degeneration in progressive muscular dystrophy. The various cellular components of bone marrow enhance the stimulation of satellite cells, which are the progenitor cells for the formation of muscle cells.
The underlying mechanisms could explain the ability of stem cells to bring about repair of the damaged muscles in muscular dystrophy.
Paracrine activity : Stem cells release various chemical messengers, growth factors which are responsible for indirect repair
Stimulation of satellite cells: The released chemical messengers stimulate the already existing “satellite cells” in the damaged muscles
Angiogenesis: In Muscular Dystrophy, due to deficiency of the protein there is impaired blood flow and reduction of oxygen supply to the muscles. Stem cells help the formation of new blood vessels increasing both blood and oxygen flow to the damaged muscles.
Neural repair: Stem cells also help in neurogenesis which is the formation of new nerve and muscle cells.
Dystrophin production: Lack of dystrophin protein is one of the chief reasons responsible for muscle weakness in muscular dystrophy. Along with muscle, dystrophin is also essential to maintain the muscle structure and stability. Stem cells increase the dystrophin production in muscles.
Differentiation: Depending on the type of cells transplanted, they can differentiate into various cell lines, including muscle cells.
Homing: On injection, stem cells have an unique ability to migrate to the damaged tissues from the site of injection and begin the repair process.
Along with these mechanisms stem cells also reduce inflammation, improve the immune function and prevent further damage to the muscle cells. All these mechanisms together, result in a positive outcome and improved functions.
Clinical results of Cell Therapy at NeuroGen Brain and Spine Institute:-
At NeuroGen Brain and Spine Institute, Mumbai we have treated over 700 patients with Muscular Dystrophy.
In a detailed analysis of 332 patients who underwent intrathecal autologous bone marrow derived mononuclear cell transplantation. The analysis depicted that 93.98% showed improvements in symptoms such as hand function, balance, stamina and ambulatory status. 42.77% showed significant improvement, 36.14% showed moderate improvement while 15.06% showed mild improvements.
Improvements seen after stem cell therapy for MD over a period of 1week to one year
- Neck Weakness
- Truncal activity
- Fine motor activity
- Gross motor activity
- Functional Upper Limb Activity
- Functional Lower Limb Activity
Research done all over the world long with our own large clinical experience shows that stem cell therapy is a viable treatment option for muscular dystrophy and in particular for Duchenne Muscular dystrophy. Clinical improvements occur in over 90% patients and these include improvements in ambulatory status, hand functions, balance, stamina, fatigue, trunk activation and standing. Objective improvements are also seen on musculoskeletal MRIs of the limbs as well as on EMGs.
Objective improvements seen in patients with Muscular Dystrophy after Stem Cell Therapy on MRI – MSK Scans
Figure:- Pre and Post MRI Scans. (a) MRI done before stem cell therapy (b) MRI done after stem cell therapy wherein white arrows denote the muscle regeneration. Stem cells injected intrathecally migrate to the damaged muscle areas and help in repair and regeneration of the muscles, improving overall muscle functions in patients with Muscular Dystrophy.