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The first historical account of muscular dystrophy appeared in 1830, when Sir Charles Bell first wrote an essay about progressive muscle weakness that he observed in young boys. Years later, we now refer to this muscle wasting as 'muscular dystrophy'. The term 'dystrophy' is derived from the Greek word "dys" which means 'difficult' or 'faulty' and "troph" which means 'to nourish'. Muscular dystrophy (MD) refers to a group of more than 30 genetic diseases which show progressive muscle degeneration causing muscle weakness. All the muscular dystrophies are caused due to a core genetic defect. Different types are determined based on different genes and the proteins that are formed by these genes. Muscle weakness is the core symptom of muscular dystrophy which leads to various postural deviations and compensations to carry out the daily functional activities. These disorders vary in age of onset, severity, and pattern of affected muscles. All forms of muscular dystrophy grow worse as muscles progressively degenerate and weaken.
Muscular dystrophy is caused due to a defect in the genes that are responsible for making proteins essential for the structure of muscles. There are no known causes of why does the genetic defect occur. These defects can be inherited or sporadic, which means that the disorder can be passed on from one generation to another or can occur as a spontaneous defect in the genes of an individual.
Muscular Dystrophy can be inherited in following ways: -
Because of these genetic defects the proteins that are formed by these genes are either absent or less functional. The group of proteins that are affected in different muscular dystrophies are from a complex called dystrophyn sarcoglycan complex (DGC). DGC is crucial to maintain the structure of the cell wall of the muscle cell, Myocyte. Muscle degeneration occurs due to disruption of the cell wall of myocyte (muscle cell) even with day to day muscle activity. This uncontrolled degeneration leads to progressive muscle death and therefore weakness, causing muscular dystrophy. Uncontrolled muscle death is the primary cause of muscle weakness however there are many other factors that hamper muscle health.
Due to continuous muscle degeneration there is chronic inflammation which damages muscles even more. As the stem cells that make new muscle cells are exhausted there is scarring of muscles and muscle cells are replaced with fat cells or connective tissue causing contractures. In addition to the muscles of the body muscles of cell walls are also affected because of which blood supply to the muscles is affected causing more damage. Not only in the muscles but DCG is also present in various non-muscular tissue like nerves, kidneys, spleen and schwann cells. Therefore muscular dystrophies may show some neurological symptoms as well.
Depending upon impaired gene, site where the gene is located and the progression of symptoms muscular dystrophies are divided into various types.
There are nine major forms of muscular dystrophy:
|Types of Muscular Dystrophys||Age of Onset||Signs & Symptoms|
|Duchenne||2 to 6 years (most severe form of Muscular Dystrophy)||Generalised muscle weakness in all voluntary muscles ,Gower's sign positive (patient makes use of his hands to climb up on his body while getting up from floor), frequent falls while walking, poor balance in standing & walking.|
|Becker||Adolescence to early adulthood||identical to Duchenne, but less severe; progresses more slowly than Duchenne|
|Limb-girdle||Late chilhood to middle age||Muscle weakness begins with hip muscles followed by shoulder muscles, difficulty in getting up from floor & chair, difficulty in stair climbing, standing balance affection, difficulty in overhead activities.|
|Facioscapulohumeral||Childhood to early adult||Facial muscle weakness (eyelid drooping, inability to whistle, decreased facial expression), Shoulder muscle weakness|
|Myotonic||20-40 years||weakness of all muscle groups accompanied by delayed relaxation of muscles after contraction; affects face, feet, hands, and neck first.|
|Congenital||Since birth||general muscle weakness and possible joint deformities|
|Oculopharyngeal||40-70 years||affect muscles of eyelids and throat causing weakening of throat muscles, which, in time, causes inability to swallow and emaciation from lack of food|
|Distal||40-60 years||weakness and wasting of muscles of the hands, forearms, and lower legs|
|Emery-Dreifuss||Chilhood to early teens||weakness and wasting of shoulder, upper arm, and shin muscles|
Muscular Dystrophy is a disease whose cure is still unknown to mankind even though the pathology of the disease is well understood. Conventional therapy includes drug therapy and rehabilitation.
Drug Therapy: This include those drugs which slow down the progression of muscle wasting. Anabolic steroids and supplementation are commonly used. These drugs have proven to effacacious so as to preserve pulmonary function, delaying the loss of ambulation and stabilizing muscle strength. Corticosteroids may enhance myoblast proliferation and promote muscle regeneration. Alternatively, steroids may inhibit muscle degradation by stabilizing lysosomal-bound proteases or muscle cell membranes. Finally, prednisone could reduce muscle damage and necrosis through its immunosuppressive and anti-inflammatory effects.
None of the existing medicines have shown in effect on the actual pathophysiology of the disease and provide only a moderate benefit for delaying progression of the disease.
Rehabilitation: Physical therapy, occupational therapy, speech therapy and other recreational therapies play a very important role in helping the patient to go about his daily activities and increasing their own independency. The main aim of these therapies is to maintain the muscle extensibility and prevent joint contractures that lead to deformities.
Rehabilitative improve quality of life of the patients and prevent secondary complications like contractures and deformity.
Gene Therapy: The aim of the Gene Therapy is precisely to introduce these genes into the patients to normalize the gene expression and protein production. Although it might seem like an easy task, in reality it is quiet daunting due to the complexity of human genes and gene expression.Several novel strategies for replacing or repairing the defective gene are in development, with early encouraging results from animal models. In most of the gene therapies a normal gene is inserted into the genome to replace the abnormal gene causing the disease. This can be done using viral vectors, Antisense- Induced Exon Skipping or Read through Stop Codon Strategies. However, the high cost and lack of human clinical trials, makes gene therapy an apprehensive approach.
All the treatment options that are available so far provide only symptomatic treatment but fail to act at a cellular level. They fail to regenerate the wasted muscles or reverse the pathology of the disease.
Also, Muscular Dystrophy is a genetic disorder and hence no treatment can repair the core changes in the defective genetic structure.
Research is going on all through the world to treat this genetic disorder. Recent research has thrown light on the potential ability of stem cells to regenerate and repair the damaged muscle cells.Stem cells are cells that are at an early stage of development. This means they have the ability to turn into any type of cell in the body and undergo self renewal.
Under physiological conditions the ability of adult muscle to undergo regeneration is largely attributed to a distinct subpopulation of muscle cells, termed satellite cells. These cells are considered to be the main cell type involved in skeletal muscle regeneration. Stem cell therapy holds great promise as a treatment for Muscular Dystrophy by providing cells that can both deliver functional muscle proteins and replenish the stem pool.
Stem cells help counteract all the potential mechanisms that cause muscular dystrophy.
Transplanted cells have myogenic potential i.e. the cells can differentiate into a mature myocyte and therefore can repair and regenerate muscle fibers. Preclinical evidence suggests that stem cell transplantation can restore dystrophin expression in mouse model of muscular dystrophy. Such dystrophin expression can lead to formation of muscle fibers that are resistant to easy damage and degeneration. Exogenous stem cell transplantation replenishes the stem cell pool. Transplanted cells can also stimulate the resident satellite cells. In addition to the actual regeneration of muscle cells and replacement of resident stem cells, transplanted cells also exhibit numerous beneficial paracrine mechanisms. Stem cells secrete various anti-inflammatory cytokines and various growth factors that are myoprotective. Vasculoendothelial growth factor is a growth factor that promotes neoangiogenesis. In addition anti-inflammatory and neo-angiogenetic effect, cells have immunomodulatory and anti-apoptotic effects on neighboring cells. Transplanted cells also stimulate muscle plasticity and remodeling therefore prevents fibrosis . These paracrine effects are also catalyzed by exosomes secreted by MSCs.
Muscular dystrophy is an emotionally, physically and financially draining condition crippling not only the patient but others around as well. After years of research, stem cell therapy has emerged as an effective treatment option for this otherwise hopeless condition.
At, NeuroGen BSI, we have treated over 350 patients of Muscular dystrophy with 94% patients showing overall improvements in the clinical symptoms.
After transplantation our patients have shown have increased trunk muscle strength, limb strength on manual muscle testing and balance. Besides, they have also improvement in ambulation, hand function, increase in stamina and better trunk balance. Together, they make it easier for the patients to live more independently.
Our stem cell transplantation protocol does not only alter the clinical conditions of a patient, but also aims to repair and stop further progression of muscle wasting that occurs in Muscular dystrophy. This has been demonstrated by the MRI-MSK reports of these patients.
1. Can muscular dystrophy be a contagious disease?
A: No it is not a contagious disease .It is mainly a genetic disorder.
2. Is muscular dystrophy always hereditary?
A: not always. Many investigations states that about 1/3 of all boys suffering from Duchene/Beckers muscular dystrophy have no family history.
3. It is often mentioned that there are several types of Muscular Dystrophy seen in people. Which is the most common type of muscular dystrophy?
A: The most common type of muscular dystrophy is Duchene and second most common is Beckers. This is followed by limb girdle muscular dystrophy which is the third most common form.
4. What is the first sign I will notice if my child has Duchene muscular dystrophy?
A: Most parents notice that the child is not running as fast as the other kids. The child may also get up from the ground, in a different way, using his hand for support and may have difficulty in climbing stairs.
5. How is muscular dystrophy transmitted?
A: Muscular dystrophy can be transmitted from either of the parent via an affected gene.
In Duchene Muscular Dystrophy the mother is a carrier of affected gene and the disease is transmitted to the male child. Each male born to such mother is on 50% risk of being affected and each female child born is at 50% risk of being a carrier.
In myotonic dystrophy, one of the parent is the carrier.
In limb girdle muscular dystrophy: the transmission could be via a recessive gene, meaning both the parents are carrier which means that both transmit the disease. It could also be inherited as a autosomal dominant disease, that means that one defective gene is enough to manifest the problem/condition. Both male child and female child can be affected with the disease.
6. My son had Duchene muscular dystrophy, can my daughter or me be a carrier?
A: Yes. There are 50% chances of her being the carrier. Genetic testing for ascertaining it is available.
7. Can this disease be detected during pregnancy?
A: In utero diagnosis of duchene muscular dystrophy is possible, if there is history of previous child or sibling having this disease/condition is known. Chorionic villus sampling or amniocentesis followed by DNA testing (MLPA) can possibly give some answers.
8. Can muscular dystrophy be detected at birth?
A: If there is a family history and a reasonable suspicion, then maybe. However, the symptoms may not be apparent until the child is at least several years of age.
9. Will Muscular Dystrophy occur only in children?
A: Not necessary. For example facioscapulohumeral, myotonic and limb girdle muscular dystrophy begin later in life .They are slow in progression and less severe than the childhood forms.
10. What are few early signs of adult muscular dystrophy?
A: In a few instances, such as facioscapulohumeral dystrophy a weak smile or inability to whistle may indicate a beginning. Similarly, in Limb girdle muscular dystrophy weakness of shoulders and hip is seen and in case of Myotonic muscular dystrophy there is apparent weakness of feet and hand.
11. Why are muscles enlarged/big in Muscular dystrophy?
A: The muscles are replaced with fatty or fibrous tissue. This condition is known as pseudo hypertrophy.
12. What are the treatment options to help child with muscular dystrophy to prolong his walking?
A: A surgical release of tight or contracted muscle and immediately standing next day can help. Second option would be serial casting. These options can help children of muscular dystrophy to prolong walking independently.
13. Is there any other method to help my child stand and walk?
A: Regular physiotherapy/exercises can help keep the child ambulatory. Standing with the help of push knee splints and high boots is found to be effective. Surgery becomes the best option when the muscles become very tight and are not stretchable at all.
14. My child is confined to wheelchair; can surgery help him to regain his walking?
A: A surgery can help straighten the joints. Surgery becomes the best option when the muscles become very tight and are not stretchable at all. However, walking would depend on the muscle power of the lower limbs.
15. How does physiotherapy and occupational therapy help muscular dystrophy patients?
A: These therapies help in preventing contractures, keep muscles strong, help in transfer, improve efficiency of functional activities like standing, walking etc.
16. Can exercises be harmful?
A: If exercises are done beyond the patients' capacity, they can lead to deterioration. The patient should not get tired or fatigued. Ample time or rest has to be given between exercises.
17. Aquatic therapy is really coming up as a therapy option. Can swimming benefit?
A: Swimming is found to be a very good exercise for the child/patient of muscular dystrophy. It is advised to be brought into practice from a very early age. Helps to increase endurance, increases muscle strength and good work up for the respiratory and cardiac muscles.
18. What is the cause of death in muscular dystrophy?
A: Respiratory muscle weakness, leading to respiratory difficulty is the major cause of death. As the muscles weaken, the child develops scoliosis or bending of the spine. This leads to crowding of the muscles of the chest and the ribs. Cough reflex becomes hampered. Patient becomes prone to chest infection, which leads to breathing difficulty.
Cardiac muscle weakness and cardiomyopathy, leading to heart failure and is another major cause of death in muscular dystrophy patients.
19. Can stem cell therapy prolong a muscular dystrophy patient's life?
A: the aim of stem cell therapy is to strengthen the muscles, prevent or slow down the degeneration of the muscles . If the patients is ambulatory/walking, the goal is to keep them walking. This indirectly could delay respiratory muscle weakness and prevent scoliosis. This could then prolong overall life expectancy , by reducing the chances of respiratory complications.
20. How does stem cell therapy work?
A: The biological task of stem cells is to repair and regenerate damaged cells. Stem cell therapy exploits this function by administering these cells in high concentrations directly in and around the damaged tissue, where they advance its self healing and repair.
21. Are there ethical concerns surrounding adult stem cell research and therapy?
A: Bone marrow transplantation has been used successfully for genetic disorders of blood, such as sickle cell anemia, thalessemia, as well as cancers such as leukemia. Since our therapy uses these very cell, which are harvested from the patient's own body (autologous cells), there are no major ethical concerns. Ethical concerns are primarily on the use of embryonic stem cells (which we do not use).
22. Is the treatment painful?
A: The therapy is done under local anesthesia and a mild sedation. There is no significant pain or discomfort during or after the procedure.
23. Does the treatment have any side effects?
A: Stem cell therapy is minimally invasive and reasonably safe. None of our patients have shown any neurological deterioration so far in connection with the stem cell therapy itself. Some side effects, such as headache (spinal headache) lasting 3-4 days which is generally self limiting, neck/back pain, vomiting, some mild rash or pain at the site of bone marrow aspiration/stem cell injection may occur. However, like any other medical or surgical treatment unexpected complications are always a possibility. These complications may be related to the medicines given, the stem cell procedure, the anesthesia, and the rehabilitation or to any of the preexisting medical or neurological conditions.
24. How long will it take me to know that I have benefitted from the treatment?
A: Maximal improvements are seen around 3-6 months after the treatment. However, in many patients there are slow progressive improvements that continue for several months/years later. Most patients do show some immediate improvements also i.e. before the discharge, in some of their symptoms.
25. Is the transplantation of the stem cells done once or more than once?
A: The decision to do the therapy a second time is taken after seeing the progress/improvements after the first therapy. If the patients show some encouraging improvement, then the case is reviewed by the entire medical and rehabilitation team and a second treatment may be recommended. This may be done anytime between 3-6 months of the first therapy.
26. Can other treatments be taken at the same time?
A: We will review what other medications the patient is already on. In most cases we do not discontinue any already going on treatment. Please inform us about any medications you are taking beforehand.
27. How much improvement will the patient have?
A: This is difficult to predict, since this a new therapy. It depends on multiple factors such as age of patient, type of illness, duration of illness and extent of rehabilitation taken after the treatment.
At Neurogen BSI, we have treated over 350 patients of Muscular dystrophy. Over all improvements were seen in 94% patients.
We have published our results in "Cell Transplantation" - an international journal. This paper reports our clinical results in 150 patients of muscular dystrophy (DMD, LGMD, BMD) who were administered autologous BMMNC intrathecally, followed by multidisciplinary rehabilitation. Evaluation after transplantation showed improvements in the trunk muscle strength, limb strength on manual muscle testing, gait improvements, positive changes in the assessment scales such as the FIM and the Brooke and Vignos Scales
Our data is regularly published in various medical and scientific journal (available for reading on our website). You are strongly advised to study these before proceeding with treatment.
Case Report - I
Master Mugdho Roy who is 5 years old child residing in Kanchrapara, Kolkata. Mugdho is a known case ofDuchenne's Muscular Dystrophy (DMD). Since birth there were small movements on bed which Mugdho could not perform but not really noticed by his parents. His parents first noticed abnormality in their child when he was 3 years old. It all started with difficulty in climbing stairs and not being able to pull himself upright from a sitting or sleeping position, running slowly etc. He was shown to several experts in Kolkata but no one was able to diagnose him correctly and his parents did not really get a clear answer as to what exactly is wrong with their son. When Mugdho was around 4 years old, roughly in the months of August-September 2015 he was taken to a neurologist in Vellore where he was diagnosed with Duchene Muscular Dystrophy on the basis of clinical investigations. On understanding the facts related to DMD the family was sad and was facing difficulty in coping up to move forward. "By watching your growing child deteriorating, suddenly facing difficulty primarily in climbing stairs, pulling himself upright and slowly becoming little dependent on us for All Day Living Activities (ADLs) is heart wrenching" – says Mughdo's father. Mugdho's mother was shattered and emotionally affected. All the friends and family members supported them saying the god will show them the path to recovery soon.
Why suddenly Mugdho started deteriorating from an usual child and got diagnosed with life trenching disorder Duchene Muscular Dystrophy ? The answer is in the family. Mugdho's two uncles (mother's side relatives) had Muscular Dystrophy. It is from the genes of the family in which unfortunately Mugdho's mother was a carrier of that affected gene.
Mugdho's parents tried searching for the treatment overall in India, they also requested the Vellore doctors to do some treatment and cure their child. By reading an article about NeuroGen in a leading newspaper Mugdho's father and his relatives came to know about NeuroGen. They first got in touch with Dr.Nandini Gokulchandran and Dr.Alok Sharma through email and after discussing their son's case in detail they decided to come to NeuroGen in December 2015.
At NeuroGen on examination following problems were noted in Mughdo
Mugdho underwent Stem Cell Transplantation on 15th December 2015. "We were told that the stem cell therapy will take around 3-6 months to show its results. We were guided in detail in terms of therapies needs to be continued and a certain diet chart needs to be followed along with medications. Being at NeuroGen and meeting Dr.Alok Sharma and Dr.Nandini Gokulchandra gave us a lot of hope along with positive motivation to fight with my child's disorder – says Mughdo's father"
Mugdho is doing 4-5 hours of therapy in a day. Within two months after discharge Mugdho has shown tremendous improvements and has reached a near around 70% improvement stage. On following up with Mugdho's condition on telephone, we have found below improvements according to his father.
"We are shocked and happy that our son has improved, for whom other doctors had said that it is difficult to get improvements in him. Our experience with NeuroGen was good. Dr.Alok Sharma and Dr.Nandini Gokulchandran are very helpful and supportive. We have already recommended many parents with special children to consult NeuroGen for their child and try for stem cell therapy – concludes Mr.Roy (Mugdho's father).
Case Report - II
Master Shubham Baser is a 20 year old male and a known case of Muscular dystrophy. His symptoms started at 12 years of age with difficulty in walking, sitting and getting up from sitting position. When Shubham was 4 years old in the year 2000 his father noticed initial symptoms of muscle weakness in Shubham. There is a history of MUSCULAR DYSTROPHY in Shubham's maternal family and hence on realizing that there is some problem with my child Mr.Baser did not panic nor took any immediate action. After 4 years in the year 2004 when Shubham was 8 years old Mr.Baser got a complete check up done for Shubham from a neurologist and hence he was diagnosed as Muscular Dystrophy. On questioning as to why they did not take an immediate action when the moment they realized in the year 2000, the father says " MUSCULAR DYSTROPHY being a part of our family we knew that there is no treatment for this disorder and hence we went to a neurologist just to confirm the disorder after 4 years in 2004". Shubham was given medications by the doctor in Indore, on realizing that its getting worsened after few years they visited several doctors but all used to prescribe him with medications only. "We by ourselves decided to start some basic physiotherapy for Shubham but that did not last long, eventually when Shubham was 12-13 years old we stopped all his medications". Mr. and Mrs. Baser also tried ayurvedic for 2-3 years but that worked negatively for Shubham, his conditioned started deteriorating and they stopped with all the therapies, medications and ayurvedic treatment.
In the year 2015 while going through the internet for muscular dystrophy treatments Shubham and his father came across Stem Cell Therapy at NeuroGen Brain and Spine Institute in Mumbai in the month of October. They contacted NeuroGen and did a thorough discussion on phone and email with Dr.Alok Sharma and Dr.Nandini Gokulchandran.
On understanding all the details Shubham underwent Stem Cell Therapy at NeuroGen BSI in December 2015. On examination below problems were noticed:
At NeuroGen, Shubham underwent Stem Cell Therapy along with a customized rehabilitation program. The aim of the rehabilitation program was to develop dissociations and gait training, therapies to increase the strength of the affected areas without fatigue and to increase overall stamina of the patient. He was given exercises that would help him improve his balance, walking, stair climbing, rolling, posture and his grip. These exercises carried out in a systematic pattern with sufficient rest intervals to the patient. Together, the aim of the rehabilitation program was to improve his overall quality of life. Shubham and his family found new hope with NeuroGen's Stem Cell Therapy. He and his family were motivated and positive for him after going back. Physiotherapy and rehabilitation taught at NeuroGen were continued after going home.
Improvements seen in Shubham after 4 months of Stem Cell Therapy are as follows :
Shubham used to be negative before due his incapability to perform activities. Now he has become an all together a new person with a bright smile on his face. His confidence has increased and now he does all his daily tasks with enthusiasm and motivation. Fear of falling is gone. "we are very happy and satisfied with Stem Cell Therapy at NeuroGen. It has given us a hope that there is a treatment which can make my son's life easier to live. At NeuroGen all the doctors and the staff is so cooperative and helpful. The guidance we wanted since long has been received at NeuroGen. How to take care or Shubham and maintain his condition was explained to us. Shubham is doing regular physiotherapy now and is also pursuing his studies" – concludes Mr.Baser, Shubham's father.