Treatment Of Progressive Muscular Dystrophy Research Articles

Efficacy and safety of glucocorticoids in the treatment of progressive muscular dystrophy in children: a systematic review and meta-analysis.

BackgroundHormonal drug therapy has been widely used in clinical practice for the treatment of progressive muscular dystrophy (PMD). Glucocorticoids, as a common drug in the clinical treatment of PMD, have been reported in several clinical studies.MethodsChinese and English databases were respectively searched using “randomized controlled trials”, “Duchenne-type myotonic dystrophy”, “glucocorticoids”, Prednisone”, “Prednisolone”, and “Methylprednisolone”, and “Defibrotide” were used as search terms. The meta-analysis was performed using the RevMan 5.3 and Stata 13 software provided by the Cochrane system.Resultsthis study included five randomized controlled trials, all of which described the correct randomization method. There were four detailed descriptions of hidden distribution schemes. There were four literatures using blind method. Heterogeneity analysis showed that there was some heterogeneity between the results of the mean prognostic muscle strength, walking time of 9 meters, and 4 flights of stairs climbing between the glucocorticoid-treated group (the experimental group) and the placebo group (the control group). There were no significant differences between the experimental group and the control group in average muscle strength level, walking time of 9 meters and climbing time of 4 flights of stairs (MD =1.77; 95% CI: −0.95 to 4.48; P=0.20>0.05), (MD =−12.27; 95% CI: −35.94 to 11.40; P=0.31>0.01), (MD =−3.09; 95% CI: −11.16 to 4.99; P=0.45>0.05). In addition, glucocorticoid treatment significantly increased creatine kinase level in patients with PMD (MD =−0.28, 95% CI: −0.57 to 0.00; P=0.05). In terms of the incidence of adverse reactions, glucocorticoid treatment significantly increased the prognostic probability of acne, rapid hair growth, and emotional irritability in PMD patients (OR =2.40; 95% CI: 1.09 to 5.27; P=0.03<0.05), (OR =3.05; 95% CI: 1.55 to 5.99; P=0.001<0.05), (OR =4.04; 95% CI: 1.82 to 10.63; P=0.001<0.05). There was no significant difference in the incidence of prognostic depression between the experimental group and the control group (OR =5.11; 95% CI: 0.80 to 32.79; P=0.09>0.05).DiscussionThe results suggest that glucocorticoids have a significant effect on PMD patients, but to a certain extent they increase the incidence of adverse reactions in patients after treatment. However, due to the lack of complete clinical data in some ongoing studies, our conclusions may not be fully representative.

Professor LIN Guo-hua's experience in treatment of progressive muscular dystrophy with acupuncture

Professor LIN Guo-hua's experience is introduced in treatment of progressive muscular dystrophy with acupuncture. It is believed that the pathogenesis of this disease is related to spleen and kidney deficiency, qi and blood insufficiency and malnutrition of tendon and muscle. The treatment is determined in terms of the pathogenesis and focuses on the regulation of spleen and kidney functions. The thinking of treatment is summarized as exerting the strong stimulation of acupuncture specially at the acupoints on the head, supplementing the sea of marrow, adjusting simultaneously the three yang meridians, rather than treating particularly yangming meridian and regulating qi in priority and considering the lung function for wei (flaccid) syndrome. Moreover, in clinical treatment, the acupoint thread-embedding therapy is commonly combined to ensure the significant therapeutic effect.

Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1) human umbilical cord tissue (hUCT) MSCs into the caudal vein of SJL mice; (2) hUCT and canine umbilical cord vein (cUCV) MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies.

Human Multipotent Mesenchymal Stromal Cells from Distinct Sources Show Different In Vivo Potential to Differentiate into Muscle Cells When Injected in Dystrophic Mice

Limb-girdle muscular dystrophies are a heterogeneous group of disorders characterized by progressive degeneration of skeletal muscle caused by the absence or deficiency of muscle proteins. The murine model of Limb-Girdle Muscular Dystrophy 2B, the SJL mice, carries a deletion in the dysferlin gene. Functionally, this mouse model shows discrete muscle weakness, starting at the age of 4-6 weeks. The possibility to restore the expression of the defective protein and improve muscular performance by cell therapy is a promising approach for the future treatment of progressive muscular dystrophies (PMD). We and others have recently shown that human adipose multipotent mesenchymal stromal cells (hASCs) can differentiate into skeletal muscle when in contact with dystrophic muscle cells in vitro and in vivo. Umbilical cord tissue and adipose tissue are known rich sources of multipotent mesenchymal stromal cells (MSCs), widely used for cell-based therapy studies. The main objective of the present study is to evaluate if MSCs from these two different sources have the same potential to reach and differentiate in muscle cells in vivo or if this capability is influenced by the niche from where they were obtained. In order to address this question we injected human derived umbilical cord tissue MSCs (hUCT MSCs) into the caudal vein of SJL mice with the same protocol previously used for hASCs; we evaluated the ability of these cells to engraft into recipient dystrophic muscle after systemic delivery, to express human muscle proteins in the dystrophic host and their effect in functional performance. These results are of great interest for future therapeutic application.

Functional improvement of patients with progressive muscular dystrophy by bone marrow and umbilical cord blood mesenchymal stem cell transplantations

To investigate the feasibility of employing double transplantations of autologous bone marrow mesenchymal stem cells (BMSC) and umbilical cord mesenchymal stem cells (UMSC) in the treatment of progressive muscular dystrophy (PMD). A total of 82 cases were treated by the double transplantations of BMSC and CB-MSC. They were diagnosed by clinical manifestations, CK, LDH, genetic analysis, electromyography, MRI and pathologic examination of biopsied muscle specimens from July 2007 to July 2008. Control group was self-made at before and after treatment and cases were followed up for 3 - 12 months. treatment method: Eighty-two patients underwent the double transplantations of bone mesenchymal stem cell (BMSC) and human umbilical cord blood MSC (CB-MSC). (1) BMSC: 80 - 150 ml bone marrow sample was collected through a puncture at bilateral posterior superior iliac spine. Ficoll density gradient centrifuge was employed to separate individual monocyte for induced differentiation. (2) CB-MSC: 80 - 160 ml umbilical cord blood was harvested and processed likewise as above. (3) Stem cell transplantation: Both BMSC and CB-MSC were collected and prepared into 1 x 10(8)/ml and 1 x 10(7)/ml cell suspension respectively. They were transplanted in divided does into the extremity muscle and vein. The clinical and laboratory parameters were monitored at 3, 6, 9 and 12 months. It was found that 31 cases (37.8%) obtained a remarkable efficacy, 37 cases (45.1%) were effective and 14 cases (17.1%) had no change. Total effective rate was 82.9%. Seventy patients (85.4%) felt limbs warmly, appetite improved, gained weight, had better appetite and action were nimble. Activity of daily living scale (ADL) in 72 patients (87.8%) increased as compared with pre-treatment (P < 0.01). LDH decreased at post-treatment [(475 +/- 223) u/L vs (410 +/- 216) u/L, P < 0.05, t = 6.650]. Creatine kinase [(2952 +/- 2259) u/L vs (2841 +/- 2092) u/L, P = 0.223, t = 1.094] and creatine [(26 +/- 12) micromol/L vs (25 +/- 11) micromol/L, P = 0.306, t = 1.029] decreased slightly. Adherence to therapy among Children and no adverse reaction was reported during the course of treatment. The double transplantation of BMSC and CB-MSC is convenient, safe and effective in the treatment of progressive muscular dystrophy and can be considered as a new therapy of PMD. MSC represents a possible tool of cellular therapeutics for PMD.

New perspectives in the treatment of progressive muscular dystrophies

New perspectives in the treatment of progressive muscular dystrophies

Hereditary muscular dystrophy in MDX mice as a homologous model for introduction of cell technologies in the treatment of progressive muscular dystrophies in humans

Hereditary muscular dystrophy in MDX mice as a homologous model for introduction of cell technologies in the treatment of progressive muscular dystrophies in humans

Hereditary muscular dystrophy in mdx mice as a homologous model for introduction of cell technologies in the treatment of progressive muscular dystrophies in humans

Hereditary muscular dystrophy in mdx mice as a homologous model for introduction of cell technologies in the treatment of progressive muscular dystrophies in humans

Hereditary muscular dystrophy in MDX mice as a homologous model for introduction of cell technologies in the treatment of progressive muscular dystrophies in humans

Life-time monitoring of the main clinical and laboratory manifestations of hereditary muscular dystrophy in mdx mice confirmed the presence of mutation in exon 23 of dystrophin gene and the absence of this protein in skeletal muscles of mutant animals. Muscular dystrophy in mice was similar to human progressive muscle disorder, which allows the use of this model for the development of cell technologies for the treatment of hereditary muscular diseases in humans.

Pathogenesis of progressive muscular dystrophy: studies on free radical metabolism in an animal model.

Evidence to suggest the presence of abnormal metabolism of oxygen free radicals in progressive muscular dystrophy is presented using an animal model. In the superficial pectoral muscles of dystrophic chickens, enzyme activities regulating the metabolism of oxygen free radicals, i.e., catalase, superoxide dismutases and glutathione peroxidase, were significantly elevated within 1 week of hatching. Activities of related enzymes, i.e., glutathione reductase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase were also elevated. In contrast, the specific activity of phosphofructokinase, the rate-limiting enzyme of the glycolytic pathway, was normal during the first 4-week period. These results suggest that there is an increased turnover of oxygen free radicals in the dystrophic muscle. This concept appears important in a further investigation of the pathogenesis and treatment of progressive muscular dystrophies.

ANABOLIC STEROIDS AND DIGITOXIN IN THE TREATMENT OF PROGRESSIVE MUSCULAR DYSTROPHY.

SummaryA total number of 51 cases of progressive muscular dystrophy were treated in two groups: one group received 19‐norandrostenolone‐decanoate together with digitoxin over a period of 3 months, a second group was treated with the steroid alone over a period of 3–5 months. The doses for the steroid were 50 mg per week, for digitoxin 0.1 mg daily.In the first group (steroid +digitoxin) of 21 cases. Controls of 15 different enzymes in muscle tissue showed a decline in activity in all of the enzyincs. The depletion of muscle enzymes was significant for CPK, GOT, GPT, ICDH and LDH. At the same time, a significant raise in serum enzyme activity could be demonstrated for ALD and CPK in the Duchennc‐typc and for ALD, CPK and LDH in the other more benign types of the disease.In the second group (steroid only) clinical observation revealed no functional improvement. I n some of the Duchenne cases the physical weakness was slightly accelerated. Laboratory findings showed no demonstrable changes in histopathology in this group. The increase of serum enzyme activitics was not Significant. MDH show‐ ed a significant fall in activity. Changes in tissue enzyme activities were not typical.I n none of the groups a raise of extractable muscle protein was seen. I n addition to rather severe virilizing effects in most of the cases, an increase of joint‐contractures in some of the cases of both groups could be observed. The increase of serum enzymes under the treatment with the steroid which can only be explained by enhanced loss of enzyme proteins from the diseased muscle tissue as a result of the increasing cell permeabilky becumes most obvious and significant when the steroid treatment is combined with digi‐ toxin. The study demonstrates that the treatment of progressive muscular dystro‐ phy with 19‐nd shows no use and involves unfavorable side effects while the combined use of the steroid with digitoxin leads to a clear and significant acceleration of the process of muscle wasting.

Treatment of Progressive Muscular Dystrophy by ATP-Na Salts

Treatment of Progressive Muscular Dystrophy by ATP-Na Salts