A Comparative Study of Strategies for Management of Duchenne Myopathy in Assiut University Children Hospital View Homepage


Ontology type: schema:MedicalStudy     


Clinical Trial Info

YEARS

2018-2021

ABSTRACT

1. Comparing different lines of treatment of Duchenne Myopathy (DM) and assessment of new lines of treatment (mesenchymal stem cell, phosphodiesterase inhibitors) in reducing the impact of disability in the patients with Duchenne Myopathy and slowing the progression of cardiomyopathy 2. Upsetting and implementation of the best treatment plan for those children with Duchenne myopathy which is suitable for the available resources in Assiut University Children Hospital Detailed Description Duchenne muscular dystrophy(DMD) is the most commonly inherited pediatric muscular disorder. It is an X-linked genetic progressive and degenerative myopathy characterized by progressive weakness, which can lead to loss of motor functions in puberty as well as cardiac,respiratory involvement and premature death. The disease is one of a group of myopathies that differ depending on the degree of severity and the affected muscle types. It occurs at a rate of approximately 1:3500 male births and arises due to spontaneous mutations in the Dystrophin gene (locus Xp21.2); 65% of causative mutations are intragenic deletions, 6-10% are intragenic duplications and 30-35% are point mutations (along with other sequence variations). The disease is caused by a deficiency of Dystrophin or the synthesis of functionally impotent Dystrophin, a critical protein component of the Dystrophin glycoprotein complex acting as a link between the cytoskeleton and the extracellular matrix in skeletal and cardiac muscles. A consequence of Dystrophin glycoprotein complex inefficiency is muscle fragility, contraction-induced damage, necrosis and inflammation. Glucocorticoid can prolong ambulation by 2 to 3 years, reduce scoliosis, and temper pulmonary and cardiac decline in the second decade of life. However, glucocorticoids causes well-known side effects, which are intolerable in more than 25% of patients. Thus, a disease-specific treatment is a major unmet need. Investigators have proposed various possibilities for the beneficial effects of corticosteroid based mainly on observations in mouse models of muscular dystrophy and on a limited number of studies in patients. These possibilities include 1. Reducing cytotoxic T lymphocytes 2. Increasing Laminin expression and myogenic repair 3. Retarding muscle apoptosis and cellular infiltration 4. Enhancing Dystrophin expression 5. Affecting neuromuscular transmission Some patients with Duchenne Myopathy treated early with steroids appear to have an improved long-term prognosis in muscle, myocardial outcome, and can help keep patients ambulatory for more years than expected without treatment. One protocol gives prednisone (0.75 mg/kg/day) for the 1st 10 days of each month to avoid chronic complications. Deflazacort, administered as 0.9 mg/kg/day, may be more effective than prednisone. The American Academy of Neurology and the Child Neurology Society recommend administering corticosteroids during the ambulatory stage of the disease.Published recommendations suggest starting therapy between 2 and 5 years of age in boys whose strength has plateaued or is declining, but earlier treatment may be more beneficial. Skeletal muscle has a great capacity to regenerate following muscle wasting caused by trauma or disease.This regenerative potential is attributed primarily to skeletal-muscle resident stem cells called satellite cells. In Duchenne Myopathy, satellite cells are exhausted following many rounds of muscle degeneration and regeneration. Hence, satellite cells and their progeny (myoblasts) have been considered as a promising candidate for cell replacement therapy for DMD and other types of muscle disease. Small quantities of adult stem cells exist in most tissues throughout the body where they remain quiescent for long periods of time prior to being activated in response to disease or tissue injury. Adult stem cells can be isolated from cells of the hematopoietic, neural, dermal, muscle and hepatic systems. Adult stem cells give rise to cell types of the tissue from which they originated, but according to scientific reports, they can differentiate into lineages other than their tissue of origin, e.g. transplanted bone marrow or enriched hematopoietic stem cells (HSCs) were reported to give rise to cells of the mesoderm, endoderm and ectoderm. Two main types of stem cells usually derived from adult bone marrow are HSCs and mesenchymal stem cells (MSC). They can sometimes be obtained from fat, skin, periosteum, synovial membrane and muscle as well. MSCs are multipotent and capable of differentiating into several connective tissue types including osteocytes, chondrocytes, adipocytes, tenocytes and myoblasts. They can also impose an additional anti-inflammatory and paracrine effect on differentiation and tissue regeneration via cytokine pathways and have anti-apoptotic features. These genetically determined pluripotent cells may be easily isolated from bone marrow because they have membrane proteins (marker called cluster of differentiation (CD34 +) and specific marker STRO-I). Compared with pluripotent embryonic stem cells or induced pluripotent stem cells, mesenchymal stem cell have a greater biosafety profile and lower risk of tumorigenicity, and perhaps that is why numerous -mesenchymal stem cell based therapies have made it to the clinical trial stage. Stem cell based therapies for the treatment of Duchenne Myopathy can proceed via two strategies. The first is autologous stem cell transfer involving cells from a patient with Duchenne Myopathy that are genetically altered in vitro to restore dystrophin expression and are subsequently re-implanted. The second is allogenic stem cell transfer, containing cells from an individual with functional dystrophin, which are transplanted into a dystrophic patient. Intramuscular route of administration can be considered most appropriate as muscular dystrophy is primarily a muscle disease. The cells can be injected in several points in the muscle alternatively they can be injected in the motor point of the muscle. A motor point is the point at which the motor branch of the innervating nerve enters the muscle. It is the point with the highest concentration of motor endplates and myoneural synapses. Due to high numbers of neuromuscular junctions at this point, a muscle contraction can be easily elicited using minimal electric stimulus. Motor points can therefore be identified as superficial points directly over the points on the muscles with help of external electrical stimulation. Limitation of this method is that only superficial muscles can be stimulated using this method. In an open study, Sharma and colleagues demonstrated the efficacy of autologous bone marrow mononuclear transplantation by intramuscularly to patients with Duchenne Myopathy, Becker muscular dystrophy and limb girdle muscular dystrophy. However, they did not provide the molecular diagnosis of these dystrophies. No significant adverse events were noted. An increase in trunk muscle strength was seen in 53% of the cases, 48% showed an increase in upper limb strength, 59% showed an increase in lower limb strength and approximately 10% showed improved gait. Eighty seven percent of 150 patients had functional improvement upon physical examination and electromyogram studies after 12 month. More... »

URL

https://clinicaltrials.gov/show/NCT03633565

Related SciGraph Publications

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/3120", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/2995", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "type": "DefinedTerm"
      }
    ], 
    "description": "1. Comparing different lines of treatment of Duchenne Myopathy (DM) and assessment of new lines of treatment (mesenchymal stem cell, phosphodiesterase inhibitors) in reducing the impact of disability in the patients with Duchenne Myopathy and slowing the progression of cardiomyopathy 2. Upsetting and implementation of the best treatment plan for those children with Duchenne myopathy which is suitable for the available resources in Assiut University Children Hospital\n\nDetailed Description\nDuchenne muscular dystrophy(DMD) is the most commonly inherited pediatric muscular disorder. It is an X-linked genetic progressive and degenerative myopathy characterized by progressive weakness, which can lead to loss of motor functions in puberty as well as cardiac,respiratory involvement and premature death. The disease is one of a group of myopathies that differ depending on the degree of severity and the affected muscle types. It occurs at a rate of approximately 1:3500 male births and arises due to spontaneous mutations in the Dystrophin gene (locus Xp21.2); 65% of causative mutations are intragenic deletions, 6-10% are intragenic duplications and 30-35% are point mutations (along with other sequence variations). The disease is caused by a deficiency of Dystrophin or the synthesis of functionally impotent Dystrophin, a critical protein component of the Dystrophin glycoprotein complex acting as a link between the cytoskeleton and the extracellular matrix in skeletal and cardiac muscles. A consequence of Dystrophin glycoprotein complex inefficiency is muscle fragility, contraction-induced damage, necrosis and inflammation. Glucocorticoid can prolong ambulation by 2 to 3 years, reduce scoliosis, and temper pulmonary and cardiac decline in the second decade of life. However, glucocorticoids causes well-known side effects, which are intolerable in more than 25% of patients. Thus, a disease-specific treatment is a major unmet need. Investigators have proposed various possibilities for the beneficial effects of corticosteroid based mainly on observations in mouse models of muscular dystrophy and on a limited number of studies in patients. These possibilities include 1. Reducing cytotoxic T lymphocytes 2. Increasing Laminin expression and myogenic repair 3. Retarding muscle apoptosis and cellular infiltration 4. Enhancing Dystrophin expression 5. Affecting neuromuscular transmission Some patients with Duchenne Myopathy treated early with steroids appear to have an improved long-term prognosis in muscle, myocardial outcome, and can help keep patients ambulatory for more years than expected without treatment. One protocol gives prednisone (0.75 mg/kg/day) for the 1st 10 days of each month to avoid chronic complications. Deflazacort, administered as 0.9 mg/kg/day, may be more effective than prednisone. The American Academy of Neurology and the Child Neurology Society recommend administering corticosteroids during the ambulatory stage of the disease.Published recommendations suggest starting therapy between 2 and 5 years of age in boys whose strength has plateaued or is declining, but earlier treatment may be more beneficial. Skeletal muscle has a great capacity to regenerate following muscle wasting caused by trauma or disease.This regenerative potential is attributed primarily to skeletal-muscle resident stem cells called satellite cells. In Duchenne Myopathy, satellite cells are exhausted following many rounds of muscle degeneration and regeneration. Hence, satellite cells and their progeny (myoblasts) have been considered as a promising candidate for cell replacement therapy for DMD and other types of muscle disease. Small quantities of adult stem cells exist in most tissues throughout the body where they remain quiescent for long periods of time prior to being activated in response to disease or tissue injury. Adult stem cells can be isolated from cells of the hematopoietic, neural, dermal, muscle and hepatic systems. Adult stem cells give rise to cell types of the tissue from which they originated, but according to scientific reports, they can differentiate into lineages other than their tissue of origin, e.g. transplanted bone marrow or enriched hematopoietic stem cells (HSCs) were reported to give rise to cells of the mesoderm, endoderm and ectoderm. Two main types of stem cells usually derived from adult bone marrow are HSCs and mesenchymal stem cells (MSC). They can sometimes be obtained from fat, skin, periosteum, synovial membrane and muscle as well. MSCs are multipotent and capable of differentiating into several connective tissue types including osteocytes, chondrocytes, adipocytes, tenocytes and myoblasts. They can also impose an additional anti-inflammatory and paracrine effect on differentiation and tissue regeneration via cytokine pathways and have anti-apoptotic features. These genetically determined pluripotent cells may be easily isolated from bone marrow because they have membrane proteins (marker called cluster of differentiation (CD34 +) and specific marker STRO-I). Compared with pluripotent embryonic stem cells or induced pluripotent stem cells, mesenchymal stem cell have a greater biosafety profile and lower risk of tumorigenicity, and perhaps that is why numerous -mesenchymal stem cell based therapies have made it to the clinical trial stage. Stem cell based therapies for the treatment of Duchenne Myopathy can proceed via two strategies. The first is autologous stem cell transfer involving cells from a patient with Duchenne Myopathy that are genetically altered in vitro to restore dystrophin expression and are subsequently re-implanted. The second is allogenic stem cell transfer, containing cells from an individual with functional dystrophin, which are transplanted into a dystrophic patient. Intramuscular route of administration can be considered most appropriate as muscular dystrophy is primarily a muscle disease. The cells can be injected in several points in the muscle alternatively they can be injected in the motor point of the muscle. A motor point is the point at which the motor branch of the innervating nerve enters the muscle. It is the point with the highest concentration of motor endplates and myoneural synapses. Due to high numbers of neuromuscular junctions at this point, a muscle contraction can be easily elicited using minimal electric stimulus. Motor points can therefore be identified as superficial points directly over the points on the muscles with help of external electrical stimulation. Limitation of this method is that only superficial muscles can be stimulated using this method. In an open study, Sharma and colleagues demonstrated the efficacy of autologous bone marrow mononuclear transplantation by intramuscularly to patients with Duchenne Myopathy, Becker muscular dystrophy and limb girdle muscular dystrophy. However, they did not provide the molecular diagnosis of these dystrophies. No significant adverse events were noted. An increase in trunk muscle strength was seen in 53% of the cases, 48% showed an increase in upper limb strength, 59% showed an increase in lower limb strength and approximately 10% showed improved gait. Eighty seven percent of 150 patients had functional improvement upon physical examination and electromyogram studies after 12 month.", 
    "endDate": "2021-11-01T00:00:00Z", 
    "id": "sg:clinicaltrial.NCT03633565", 
    "keywords": [
      "comparative study", 
      "management", 
      "duchenne", 
      "different line", 
      "assessment", 
      "Mesenchymal Stromal Cell", 
      "phosphodiesterase inhibitor", 
      "disability", 
      "patient", 
      "implementation", 
      "treatment plan", 
      "child", 
      "available resource", 
      "hospital", 
      "Duchenne muscular dystrophy", 
      "pediatrics", 
      "progressive weakness", 
      "motor function", 
      "puberty", 
      "involvement", 
      "Premature Mortality", 
      "disease", 
      "Muscular Disease", 
      "severity", 
      "affected muscle", 
      "male birth", 
      "spontaneous mutation", 
      "dystrophin gene", 
      "locus", 
      "causative mutation", 
      "deletion", 
      "duplication", 
      "point mutation", 
      "sequence variation", 
      "deficiency", 
      "dystrophin", 
      "synthesis", 
      "protein component", 
      "dystrophin-glycoprotein complex", 
      "cytoskeleton", 
      "extracellular matrix", 
      "skeletal and cardiac muscle", 
      "consequence", 
      "fragility", 
      "contraction", 
      "necrosis", 
      "inflammation", 
      "glucocorticoid", 
      "Walking", 
      "scoliosis", 
      "temper", 
      "decline", 
      "second decade", 
      "life", 
      "known side effect", 
      "disease-specific treatment", 
      "major unmet need", 
      "possibility", 
      "beneficial effect", 
      "corticosteroid", 
      "observation", 
      "mouse model", 
      "muscular dystrophy", 
      "limited number", 
      "cytotoxic T lymphocyte", 
      "expression", 
      "repair", 
      "retarding", 
      "infiltration", 
      "neuromuscular transmission", 
      "steroid", 
      "long-term prognosis", 
      "muscle", 
      "protocol", 
      "prednisone", 
      "chronic complication", 
      "American Academy of Neurology", 
      "child neurology", 
      "stage", 
      "recommendation", 
      "therapy", 
      "age", 
      "boy", 
      "skeletal muscle", 
      "great capacity", 
      "muscle wasting", 
      "Wound and Injury", 
      "resident stem cell", 
      "satellite cell", 
      "round", 
      "muscle degeneration", 
      "regeneration", 
      "progeny", 
      "myoblasts", 
      "promising candidate", 
      "cell replacement therapy", 
      "muscle disease", 
      "small quantity", 
      "adult stem cell", 
      "tissue", 
      "body", 
      "long period", 
      "tissue injury", 
      "cell", 
      "rise", 
      "cell type", 
      "scientific report", 
      "lineage", 
      "origin", 
      "bone marrow", 
      "hematopoietic stem cell", 
      "Mesoderm", 
      "endoderm", 
      "ectoderm", 
      "main type", 
      "stem cell", 
      "adult bone marrow", 
      "skin", 
      "periosteum", 
      "Synovial Membrane", 
      "connective tissue", 
      "osteocyte", 
      "chondrocytes", 
      "adipocytes", 
      "tenocytes", 
      "paracrine effect", 
      "tissue regeneration", 
      "cytokine pathway", 
      "feature", 
      "pluripotent cell", 
      "membrane protein", 
      "cluster", 
      "CD34", 
      "specific marker", 
      "embryonic stem cell", 
      "induced pluripotent stem cell", 
      "biosafety", 
      "low risk", 
      "tumorigenicity", 
      "stem cell-based therapy", 
      "clinical trial", 
      "autologous stem cell", 
      "vitro", 
      "dystrophin expression", 
      "cell transfer", 
      "intramuscular", 
      "Organization and Administration", 
      "motor", 
      "branch", 
      "nerve", 
      "high concentration", 
      "motor endplate", 
      "Synapsis", 
      "high number", 
      "neuromuscular junction", 
      "muscle contraction", 
      "stimulus", 
      "help", 
      "stimulation", 
      "limitation", 
      "method", 
      "Sharma", 
      "colleague", 
      "efficacy", 
      "autologous bone marrow", 
      "Limb-Girdle Muscular Dystrophy", 
      "molecular diagnosis", 
      "dystrophy", 
      "significant adverse event", 
      "muscle strength", 
      "Upper", 
      "low limb", 
      "gait", 
      "eighty", 
      "functional improvement", 
      "physical examination", 
      "electromyogram"
    ], 
    "name": "A Comparative Study of Strategies for Management of Duchenne Myopathy in Assiut University Children Hospital", 
    "sameAs": [
      "https://app.dimensions.ai/details/clinical_trial/NCT03633565"
    ], 
    "sdDataset": "clinical_trials", 
    "sdDatePublished": "2019-03-07T15:28", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "file:///pack/app/us_ct_data_00028.json", 
    "sponsor": [
      {
        "id": "https://www.grid.ac/institutes/grid.252487.e", 
        "type": "Organization"
      }
    ], 
    "startDate": "2018-09-01T00:00:00Z", 
    "subjectOf": [
      {
        "id": "https://doi.org/10.1016/j.bbadis.2006.08.011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000151071"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.stem.2012.05.015", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001560895"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/79924", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003277398", 
          "https://doi.org/10.1038/79924"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1083/jcb.200108150", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003892205"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1161/01.res.0000126574.61061.25", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1008745583"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/0471142905.hg0925s83", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1009782877"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncb0901-778", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018972963", 
          "https://doi.org/10.1038/ncb0901-778"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/hep.21047", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020330328"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0022-510x(93)90017-s", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029964630"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrm3265", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037623358", 
          "https://doi.org/10.1038/nrm3265"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0140-6736(12)61897-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037683703"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0140-6736(02)07815-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041488579"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/088307380201700306", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044643089"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s11910-996-0009-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045672507", 
          "https://doi.org/10.1007/s11910-996-0009-8"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1620/tjem.192.211", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053413498"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074595714", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074644585", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1077015302", 
        "type": "CreativeWork"
      }
    ], 
    "type": "MedicalStudy", 
    "url": "https://clinicaltrials.gov/show/NCT03633565"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/clinicaltrial.NCT03633565'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/clinicaltrial.NCT03633565'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/clinicaltrial.NCT03633565'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/clinicaltrial.NCT03633565'


 

This table displays all metadata directly associated to this object as RDF triples.

254 TRIPLES      16 PREDICATES      211 URIs      186 LITERALS      1 BLANK NODES

Subject Predicate Object
1 sg:clinicaltrial.NCT03633565 schema:about anzsrc-for:2995
2 anzsrc-for:3120
3 schema:description 1. Comparing different lines of treatment of Duchenne Myopathy (DM) and assessment of new lines of treatment (mesenchymal stem cell, phosphodiesterase inhibitors) in reducing the impact of disability in the patients with Duchenne Myopathy and slowing the progression of cardiomyopathy 2. Upsetting and implementation of the best treatment plan for those children with Duchenne myopathy which is suitable for the available resources in Assiut University Children Hospital Detailed Description Duchenne muscular dystrophy(DMD) is the most commonly inherited pediatric muscular disorder. It is an X-linked genetic progressive and degenerative myopathy characterized by progressive weakness, which can lead to loss of motor functions in puberty as well as cardiac,respiratory involvement and premature death. The disease is one of a group of myopathies that differ depending on the degree of severity and the affected muscle types. It occurs at a rate of approximately 1:3500 male births and arises due to spontaneous mutations in the Dystrophin gene (locus Xp21.2); 65% of causative mutations are intragenic deletions, 6-10% are intragenic duplications and 30-35% are point mutations (along with other sequence variations). The disease is caused by a deficiency of Dystrophin or the synthesis of functionally impotent Dystrophin, a critical protein component of the Dystrophin glycoprotein complex acting as a link between the cytoskeleton and the extracellular matrix in skeletal and cardiac muscles. A consequence of Dystrophin glycoprotein complex inefficiency is muscle fragility, contraction-induced damage, necrosis and inflammation. Glucocorticoid can prolong ambulation by 2 to 3 years, reduce scoliosis, and temper pulmonary and cardiac decline in the second decade of life. However, glucocorticoids causes well-known side effects, which are intolerable in more than 25% of patients. Thus, a disease-specific treatment is a major unmet need. Investigators have proposed various possibilities for the beneficial effects of corticosteroid based mainly on observations in mouse models of muscular dystrophy and on a limited number of studies in patients. These possibilities include 1. Reducing cytotoxic T lymphocytes 2. Increasing Laminin expression and myogenic repair 3. Retarding muscle apoptosis and cellular infiltration 4. Enhancing Dystrophin expression 5. Affecting neuromuscular transmission Some patients with Duchenne Myopathy treated early with steroids appear to have an improved long-term prognosis in muscle, myocardial outcome, and can help keep patients ambulatory for more years than expected without treatment. One protocol gives prednisone (0.75 mg/kg/day) for the 1st 10 days of each month to avoid chronic complications. Deflazacort, administered as 0.9 mg/kg/day, may be more effective than prednisone. The American Academy of Neurology and the Child Neurology Society recommend administering corticosteroids during the ambulatory stage of the disease.Published recommendations suggest starting therapy between 2 and 5 years of age in boys whose strength has plateaued or is declining, but earlier treatment may be more beneficial. Skeletal muscle has a great capacity to regenerate following muscle wasting caused by trauma or disease.This regenerative potential is attributed primarily to skeletal-muscle resident stem cells called satellite cells. In Duchenne Myopathy, satellite cells are exhausted following many rounds of muscle degeneration and regeneration. Hence, satellite cells and their progeny (myoblasts) have been considered as a promising candidate for cell replacement therapy for DMD and other types of muscle disease. Small quantities of adult stem cells exist in most tissues throughout the body where they remain quiescent for long periods of time prior to being activated in response to disease or tissue injury. Adult stem cells can be isolated from cells of the hematopoietic, neural, dermal, muscle and hepatic systems. Adult stem cells give rise to cell types of the tissue from which they originated, but according to scientific reports, they can differentiate into lineages other than their tissue of origin, e.g. transplanted bone marrow or enriched hematopoietic stem cells (HSCs) were reported to give rise to cells of the mesoderm, endoderm and ectoderm. Two main types of stem cells usually derived from adult bone marrow are HSCs and mesenchymal stem cells (MSC). They can sometimes be obtained from fat, skin, periosteum, synovial membrane and muscle as well. MSCs are multipotent and capable of differentiating into several connective tissue types including osteocytes, chondrocytes, adipocytes, tenocytes and myoblasts. They can also impose an additional anti-inflammatory and paracrine effect on differentiation and tissue regeneration via cytokine pathways and have anti-apoptotic features. These genetically determined pluripotent cells may be easily isolated from bone marrow because they have membrane proteins (marker called cluster of differentiation (CD34 +) and specific marker STRO-I). Compared with pluripotent embryonic stem cells or induced pluripotent stem cells, mesenchymal stem cell have a greater biosafety profile and lower risk of tumorigenicity, and perhaps that is why numerous -mesenchymal stem cell based therapies have made it to the clinical trial stage. Stem cell based therapies for the treatment of Duchenne Myopathy can proceed via two strategies. The first is autologous stem cell transfer involving cells from a patient with Duchenne Myopathy that are genetically altered in vitro to restore dystrophin expression and are subsequently re-implanted. The second is allogenic stem cell transfer, containing cells from an individual with functional dystrophin, which are transplanted into a dystrophic patient. Intramuscular route of administration can be considered most appropriate as muscular dystrophy is primarily a muscle disease. The cells can be injected in several points in the muscle alternatively they can be injected in the motor point of the muscle. A motor point is the point at which the motor branch of the innervating nerve enters the muscle. It is the point with the highest concentration of motor endplates and myoneural synapses. Due to high numbers of neuromuscular junctions at this point, a muscle contraction can be easily elicited using minimal electric stimulus. Motor points can therefore be identified as superficial points directly over the points on the muscles with help of external electrical stimulation. Limitation of this method is that only superficial muscles can be stimulated using this method. In an open study, Sharma and colleagues demonstrated the efficacy of autologous bone marrow mononuclear transplantation by intramuscularly to patients with Duchenne Myopathy, Becker muscular dystrophy and limb girdle muscular dystrophy. However, they did not provide the molecular diagnosis of these dystrophies. No significant adverse events were noted. An increase in trunk muscle strength was seen in 53% of the cases, 48% showed an increase in upper limb strength, 59% showed an increase in lower limb strength and approximately 10% showed improved gait. Eighty seven percent of 150 patients had functional improvement upon physical examination and electromyogram studies after 12 month.
4 schema:endDate 2021-11-01T00:00:00Z
5 schema:keywords American Academy of Neurology
6 CD34
7 Duchenne muscular dystrophy
8 Limb-Girdle Muscular Dystrophy
9 Mesenchymal Stromal Cell
10 Mesoderm
11 Muscular Disease
12 Organization and Administration
13 Premature Mortality
14 Sharma
15 Synapsis
16 Synovial Membrane
17 Upper
18 Walking
19 Wound and Injury
20 adipocytes
21 adult bone marrow
22 adult stem cell
23 affected muscle
24 age
25 assessment
26 autologous bone marrow
27 autologous stem cell
28 available resource
29 beneficial effect
30 biosafety
31 body
32 bone marrow
33 boy
34 branch
35 causative mutation
36 cell
37 cell replacement therapy
38 cell transfer
39 cell type
40 child
41 child neurology
42 chondrocytes
43 chronic complication
44 clinical trial
45 cluster
46 colleague
47 comparative study
48 connective tissue
49 consequence
50 contraction
51 corticosteroid
52 cytokine pathway
53 cytoskeleton
54 cytotoxic T lymphocyte
55 decline
56 deficiency
57 deletion
58 different line
59 disability
60 disease
61 disease-specific treatment
62 duchenne
63 duplication
64 dystrophin
65 dystrophin expression
66 dystrophin gene
67 dystrophin-glycoprotein complex
68 dystrophy
69 ectoderm
70 efficacy
71 eighty
72 electromyogram
73 embryonic stem cell
74 endoderm
75 expression
76 extracellular matrix
77 feature
78 fragility
79 functional improvement
80 gait
81 glucocorticoid
82 great capacity
83 help
84 hematopoietic stem cell
85 high concentration
86 high number
87 hospital
88 implementation
89 induced pluripotent stem cell
90 infiltration
91 inflammation
92 intramuscular
93 involvement
94 known side effect
95 life
96 limitation
97 limited number
98 lineage
99 locus
100 long period
101 long-term prognosis
102 low limb
103 low risk
104 main type
105 major unmet need
106 male birth
107 management
108 membrane protein
109 method
110 molecular diagnosis
111 motor
112 motor endplate
113 motor function
114 mouse model
115 muscle
116 muscle contraction
117 muscle degeneration
118 muscle disease
119 muscle strength
120 muscle wasting
121 muscular dystrophy
122 myoblasts
123 necrosis
124 nerve
125 neuromuscular junction
126 neuromuscular transmission
127 observation
128 origin
129 osteocyte
130 paracrine effect
131 patient
132 pediatrics
133 periosteum
134 phosphodiesterase inhibitor
135 physical examination
136 pluripotent cell
137 point mutation
138 possibility
139 prednisone
140 progeny
141 progressive weakness
142 promising candidate
143 protein component
144 protocol
145 puberty
146 recommendation
147 regeneration
148 repair
149 resident stem cell
150 retarding
151 rise
152 round
153 satellite cell
154 scientific report
155 scoliosis
156 second decade
157 sequence variation
158 severity
159 significant adverse event
160 skeletal and cardiac muscle
161 skeletal muscle
162 skin
163 small quantity
164 specific marker
165 spontaneous mutation
166 stage
167 stem cell
168 stem cell-based therapy
169 steroid
170 stimulation
171 stimulus
172 synthesis
173 temper
174 tenocytes
175 therapy
176 tissue
177 tissue injury
178 tissue regeneration
179 treatment plan
180 tumorigenicity
181 vitro
182 schema:name A Comparative Study of Strategies for Management of Duchenne Myopathy in Assiut University Children Hospital
183 schema:sameAs https://app.dimensions.ai/details/clinical_trial/NCT03633565
184 schema:sdDatePublished 2019-03-07T15:28
185 schema:sdLicense https://scigraph.springernature.com/explorer/license/
186 schema:sdPublisher N207dd40942474fa5b6adf1a7113f8ff1
187 schema:sponsor https://www.grid.ac/institutes/grid.252487.e
188 schema:startDate 2018-09-01T00:00:00Z
189 schema:subjectOf sg:pub.10.1007/s11910-996-0009-8
190 sg:pub.10.1038/79924
191 sg:pub.10.1038/ncb0901-778
192 sg:pub.10.1038/nrm3265
193 https://app.dimensions.ai/details/publication/pub.1074595714
194 https://app.dimensions.ai/details/publication/pub.1074644585
195 https://app.dimensions.ai/details/publication/pub.1077015302
196 https://doi.org/10.1002/0471142905.hg0925s83
197 https://doi.org/10.1002/hep.21047
198 https://doi.org/10.1016/0022-510x(93)90017-s
199 https://doi.org/10.1016/j.bbadis.2006.08.011
200 https://doi.org/10.1016/j.stem.2012.05.015
201 https://doi.org/10.1016/s0140-6736(02)07815-7
202 https://doi.org/10.1016/s0140-6736(12)61897-2
203 https://doi.org/10.1083/jcb.200108150
204 https://doi.org/10.1161/01.res.0000126574.61061.25
205 https://doi.org/10.1177/088307380201700306
206 https://doi.org/10.1620/tjem.192.211
207 schema:url https://clinicaltrials.gov/show/NCT03633565
208 sgo:license sg:explorer/license/
209 sgo:sdDataset clinical_trials
210 rdf:type schema:MedicalStudy
211 N207dd40942474fa5b6adf1a7113f8ff1 schema:name Springer Nature - SN SciGraph project
212 rdf:type schema:Organization
213 anzsrc-for:2995 schema:inDefinedTermSet anzsrc-for:
214 rdf:type schema:DefinedTerm
215 anzsrc-for:3120 schema:inDefinedTermSet anzsrc-for:
216 rdf:type schema:DefinedTerm
217 sg:pub.10.1007/s11910-996-0009-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045672507
218 https://doi.org/10.1007/s11910-996-0009-8
219 rdf:type schema:CreativeWork
220 sg:pub.10.1038/79924 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003277398
221 https://doi.org/10.1038/79924
222 rdf:type schema:CreativeWork
223 sg:pub.10.1038/ncb0901-778 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018972963
224 https://doi.org/10.1038/ncb0901-778
225 rdf:type schema:CreativeWork
226 sg:pub.10.1038/nrm3265 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037623358
227 https://doi.org/10.1038/nrm3265
228 rdf:type schema:CreativeWork
229 https://app.dimensions.ai/details/publication/pub.1074595714 schema:CreativeWork
230 https://app.dimensions.ai/details/publication/pub.1074644585 schema:CreativeWork
231 https://app.dimensions.ai/details/publication/pub.1077015302 schema:CreativeWork
232 https://doi.org/10.1002/0471142905.hg0925s83 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009782877
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1002/hep.21047 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020330328
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1016/0022-510x(93)90017-s schema:sameAs https://app.dimensions.ai/details/publication/pub.1029964630
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1016/j.bbadis.2006.08.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000151071
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1016/j.stem.2012.05.015 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001560895
241 rdf:type schema:CreativeWork
242 https://doi.org/10.1016/s0140-6736(02)07815-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041488579
243 rdf:type schema:CreativeWork
244 https://doi.org/10.1016/s0140-6736(12)61897-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037683703
245 rdf:type schema:CreativeWork
246 https://doi.org/10.1083/jcb.200108150 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003892205
247 rdf:type schema:CreativeWork
248 https://doi.org/10.1161/01.res.0000126574.61061.25 schema:sameAs https://app.dimensions.ai/details/publication/pub.1008745583
249 rdf:type schema:CreativeWork
250 https://doi.org/10.1177/088307380201700306 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044643089
251 rdf:type schema:CreativeWork
252 https://doi.org/10.1620/tjem.192.211 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053413498
253 rdf:type schema:CreativeWork
254 https://www.grid.ac/institutes/grid.252487.e schema:Organization
 




Preview window. Press ESC to close (or click here)


...