Abstract

Becker’s Muscular Dystrophy (BMD) is a dystrophinopathy manifested as progressive muscle degeneration. Autologous Bone Marrow Mononuclear Cells (BMMNCs) have shown some myogenic potential. The paracrine effects of the BMMNCs reduce the inflammation and are thought to reduce muscle degeneration. We treated a 39 year old dental surgeon suffering fromBMD. Muscle strength was reduced when measured using modified Medical Research Council’s Manual Muscle Testing (mMRC-MMT). Static sitting balance was poor. He was wheelchair dependent for ambulation and moderately independent in Activities of Daily Living (ADL). Functional Independence Measure (FIM) score was 93. Musculoskeletal Magnetic Resonance Imaging (MRI-MSK) showed moderate fatty infiltration in the muscles. Three cellular transplantations were carried out. Clinical assessment and the investigations were repeated. Progressive increase in the muscle strength was noted. Ambulation was independent using push-knee splints and minimal assistance when weary. Static and dynamic balance in sitting and standing improved. FIM score increased from 93 to 105. There was no increase in the degree of fatty infiltration, as seen on the MRI-MSK. The case study provides evidence for the putative benefits of cellular therapy in altering the disease progression in BMD. It also suggests augmented clinical benefits of combination of cellular therapy and rehabilitation. Read more...

Abstract

Muscular dystrophy is a genetic disorder with no definite cure. A study was carried out on 150 patients diagnosed with muscular dystrophy. These included Duchenne muscular dystrophy, limb-girdle muscular dystrophy, and Becker muscular dystrophy variants. They were administered autologous bonemarrow-derived mononuclear cells intrathecally and intramuscularly at the motor points of the antigravity weak muscles followed by  vigorous rehabilitation therapy. No significant adverse events were noted. Assessment after transplantation showed neurological improvements in trunk muscle strength, limb strength on manual muscle testing, gait improvements, and a favorable shift on assessment scales such as the Functional Independence Measure and the Brooke and Vignos Scales. Furthermore, imaging and electrophysiological studies also showed significant changes in selective cases. On a mean follow-up of 12 ± 1 months, overall 86.67% cases showed symptomatic and functional improvements, with six patients showing changes with respect to muscle regeneration and a decrease in fatty infiltration on musculoskeletal magnetic resonance imaging and nine showing improved muscle electrical activity on electromyography. Fifty-three percent of the cases showed an increase in trunk muscle  strength, 48% showed an increase in upper limb strength, 59% showed an increase in lower limb strength, and approximately 10% showed improved gait. These data were statistically analyzed using Student’s paired t test and found to be significant. The results show that this treatment is safe and efficacious and also improves the quality of life of patients having muscular dystrophy. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation. Read more...

Abstract

Duchenne muscular dystrophy (DMD) is a fatal, genetic, progressive, degenerating muscle disorder. Current treat-ment options are palliative. Newer options of cellular therapy promise to alter the disease process. Preclinical studies have successfully tested myogenic, neurogenic potential and dystrophin expression of bone marrow mononuclear cells. We treated a 9-year-old boy suffering from DMD with serial autologous bone marrow mononuclear cell transplantations followed by multidisciplinary rehabilitation. Brooke-Vignos score was 10 and he was wheelchairbound. Over 36 months, gradual progressive improvement was noticed in muscle strength, ambulation with  assistive devices, fine motor movements, Brooke-Vignos score, and functional independence measure score.  Nine months after the transplantation, electromyography findings showed development of new normal motor  unit potentials of the vastus medialis muscle. Magnetic resonance imaging scan of musculoskeletal systems showed no increase in fatty infiltration. This case report provides early investigative findings or the restorative effects of cellular therapy in DMD. Read more...

Abstract

Duchenne muscular dystrophy (DMD) is the most common childhood muscular dystrophy. Presently, there is no known cure for the disorder. We report an 18-year-old boy with DMD who underwent autologous bone marrow-derived mononuclear cell transplantation intrathecally as well as intramuscularly in specific muscles. The parameters used to assess the patient pre- and postoperatively were creatine phosphokinase levels, electromyography, magnetic resonance imaging (MRI) musculoskeletal system upper and lower limbs and manual muscle testing. On follow-up at six months, he showed significant functional improvements along with improvements in his muscle strength. Clinically, his MRI also showed muscle fiber regeneration with decrease in fatty infiltration. Read more...

Abstract

Dystrophinopathies are X-linked recessive disorders which includes Duchenne muscular dystrophy and Becker muscular dystrophy. Forty-six cases were included in our study. Our main aim was to identify the exon deletions in these cases, determine the extent of cardiac involvement by two dimensional echocardiography and whether a correlation exists between the two. It was found that the cases having left ventricular ejection fraction =40% majorly showed deletions in the proximal exons as compared to the distal exons. Read more...

Abstract

Limb girdle muscular dystrophy (LGMD), a group of progressive degenerative disorders, causes functional limitation affecting the quality of life. Cell therapy is being  widely explored and preliminary studies have shown beneficial effects. Cell therapy induces  trophic-factors release, angiogenesis, anti-inflammation, and protein synthesis, which helps in the reparative process at the microcellular level. In this 5-year longitudinal study, the effect of autologous bone marrow mononuclear cells is studied on the natural course of 65 patients with LGMD. Functional Independence Measure and manual muscle testing showed statistically  significant improvement, post-cell transplantation. The key finding of this study was demonstration of a plateau phase in the disease progression of the patients. No adverse events were noted. Autologous bone marrow mononuclear cells may be a novel, safe, and effective treatment approach to control the rate of progression of LGMD, thus improving the functional outcomes. Further randomized controlled trials are required. Read more...

Abstract

Becker muscular dystrophy (BMD) is an inherited disorder due to deletions of the dystrophin gene that leads to muscle weakness. Effects of bone marrow mononuclear cell (BMMNC) transplantation in Muscular Dystrophy have shown to be safe and beneficial. We treated a 20year-old male suffering from BMD with autologous BMMNC transplantation followed by multidisciplinary rehabilitation. He presented with muscle weakness and had difficulty in performing his activities. The BMMNCs were transplanted via intrathecal and intramuscular routes. The effects were measured on clinical and functional changes.  Over 9 months, gradual improvement was noticed in muscle strength, respiratory functions and North Star Ambulatory

Assessment Scale. Functional Independence Measure, Berg Balance Score, Brooke and Vignos Scale remained stable indicating halting of the progression. The case report suggests that cellular therapy combined with rehabilitation may have possibility of repairing and regenerating muscle fibers and decreasing the rate of progression of BMD.  Read more...

Abstract

Cell transplantation is emerging as a potential therapeutic option for LGMD due to its ability to aid in repair and regeneration of dystrophic muscles. Our aim was to study the benefit of autologous bone marrow mononuclear cells (BMMNCs) in LGMD.  We administered a 39 year old LGMD male with autologous BMMNCs intramuscularly and intrathecally twice followed by rehabilitation. His muscle power in all limbs was below functional level with

proximal weakness more than distal. Functional Independence Measure (FIM) score was 114. Over a period of 18 months, muscle power increased gradually with improvements in functional activities. FIM score was maintained indicating a halt in the progression of disease. 36 months after second dose of transplantation, patient's condition was maintained with no deterioration in quality of life. This report provides early evidence of beneficial effects of autologous BMMNCs coupled with rehabilitation in halting the disease progression and functional improvement in LGMD.  Read more...

Abstract

Muscular dystrophies are a heterogeneous group of genetic disorders characterized by progressive muscle degeneration of variable distribution and severity. There is no known definitive treatment. Cell therapy holds promise as an interim treatment approach that can improve the quality of life of these patients. We reviewed the published literature, assessing the safety and efficacy of autologous bone marrow mononuclear cell therapy in muscular dystrophy. An online search revealed 13 studies including 3 case series and 10 case reports with a total of 257 patients. All the preliminary studies met the prespecified criteria for quality and were of fair to good quality. All the studies administered cell therapy using intrathecal and intramuscular routes. There were no procedure related major adverse events in any of the studies. Manual muscle test,Functional Independence Measure and Brooke and Vignos scales were the most commonly used outcome measures in the studies. All the studies demonstrated improvement on functional scales and 12 studies demonstrated improvement in muscle strength post intervention. The studies showed that cell therapy using autologous bone marrow mononuclear cells is safe and effective in slowing down disease progression, and maybe an effective interim treatment option.  Read more...

Abstract

With  no  known  cure,  new  advances,  such  as  gene  therapy,  exon  skipping  and  cell  therapy  are  being explored as treatment options. Gene therapy using viral and non‐viral vectors is however, restricted due to safety issues. Although a drug, eteplirsen, has been recently approved, it is speciically indicated for patients with a mutation in the dystrophin gene that is amenable to exon 51 skipping. The ability of bone marrow mononuclear cells to replenish the stem cell pool and facilitate muscle repair, makes cell therapy with  bone  marrow  mononuclear  cells  a  promising  treatment  option  in  this  relentlessly  progressive disorder. We report a seven‐year and eight month old patient with Duchenne Muscular Dystrophy treated with serial autologous bone marrow mononuclear cell therapy offered as a last resort therapy followed by long term multi disciplinary rehabilitation. No adverse events were reported after the procedure and up  to  14  months  follow  up  duration.  Functional  improvements  were  seen  as  an  improved  North  Star Ambulatory  Assessment  score  from  18  to  20  over  a  14  month  follow‐up  period.  2‐minute  walk  test distance  improved  from  63  meters  before  the  intervention  to  85.8  meters,  10  months  post  irst  cell therapy. 6‐minute walk test distance improved from 178.2 meters at 10 months post irst cell therapy to 191.4  meters  at  14  months  post  irst  cell  therapy.  Objective  improvements  were  seen  in  the  musculo skeletal magnetic resonance imaging with the fractional anisotropy values in the posterior thigh muscles decreasing from 0.603 on the right side and 0.600 on the left side to 0.482 on the right and 0.415 on the left side. These objective and functional improvements suggest possible potential beneits of cell therapy coupled with neurorehabilitation in Duchenne muscular dystrophy and need to be explored further.

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Abstract

Limb  Girdle  Muscular  Dystrophy  (LGMD)  is  a  group  of  heterogeneous  autosomal  hereditary neuromuscular disorders resulting in progressive muscular weakness, predominantly in the proximal girdle  muscles.  Currently  the  management  of  LGMD  is  palliative  and  does  not  cure  or  alter  the disease  pathology.  Hence  there  is  a  need  of  an  intervention  that  may  be  able  to  alter  the  disease pathology.  We  present  a  case  of  a  41-year-old  female  of  LGMD  (Delta  sarcoglycanopathy)  who underwent  two  intrathecal  and  intramuscular  transplantations  of  autologous  bone  marrow mononuclear  cells  (BMMNCs)  along  with  standard  rehabilitation  at  the  interval  of  7months. Musculoskeletal  Magnetic  resonance  imaging  (MRI-MSK)  was  conducted  before  both  the transplantations. Over 13 months she showed improvements in functional outcome measures such as Bergs  balance  score,  north star  ambulatory  assessment  and  six-minute  walk test.  Her  functional independence  measure  score  was  unchanged  for  the  13  months  since  intervention.  Per  the  natural course of the disease there is progressive muscle weakness. Maintenance of functional independence, improved muscle strength as well as six-minute walk distance and maintained MRI-MSK parameters over 13 months in this patient suggest that, cellular therapy along with neurorehabilitation may alter or halt the progression of the disease in LGMD. Read more...

Abstract

Limb girdle muscular dystrophy is a heterogeneous group of genetic disorders characterized by progressive muscle weakness caused by autosomal dominant or recessive gene mutations. Although no curative treatment is currently available, adult bone marrow stem cell transplantation maybe a promising therapeutic approach in view of their capacity to regenerate muscle fibers. Musculoskeletal magnetic resonance imaging is a useful non- invasive tool to track disease progression and to test the efficacy of a treatment. We report a twenty six year old female patient diagnosed with limb girdle muscular dystrophy and treated with intrathecal and intramuscular injections of autologous bone marrow mononuclear cells followed by multidisciplinary rehabilitation. Repeat musculoskeletal magnetic resonance imaging 6 months post cell therapy, showed no further increase in fatty infiltration or loss of muscle volume in the musculature of bilateral upper and lower limbs. Objective improvements were seen on musculoskeletal resonance spectroscopy as less area under the curve in the flattened extramyocellular lipid peak with reduction in the intramyocellular (-CH2) lipid/creatine ratio in the tibialis anterior muscle in comparison to the pre-cell transplantation scan. Functional improvements were noted, along with strength improvements were noted in the bilateral hip abductors, adductors, left hip extensors, knee flexors, ankle dorsiflexors, plantar flexors, peronei, shoulder abductors and adductors, internal and external rotators, right wrist extensors, abdominals and back extensors on the modified Medical Research Council’s manual muscle testing scale with the improvements being maintained over the 9 month follow up duration. These functional improvements and positive musculoskeletal spectroscopic changes provide evidence of the disease modifying benefits of cell therapy in limb girdle muscular dystrophy. However, since these solitary results cannot be generalized to the limb girdle muscular dystrophy population, larger clinical controlled trials are needed.  Read more...

Abstract

Duchenne Muscular Dystrophy (DMD) is an X-linked inherited myopathy where there is progressive muscular degeneration due to dystrophin deficiency. To date, there are no curative treatments for DMD. Cellular therapy is a valuable adjuvant to current palliative treatments. This case report describes an 8 year old boy, with classical signs and symptoms of DMD including difficulty in walking and getting up from the floor, who received cellular therapy. Two doses of autologous bone marrow derived mononuclear cells were injected both intrathecally and intramuscularly in motor points across various large and weakened muscle groups in his body. A wide range of functional improvements were observed in the patient on follow up over a period of 12 months, like increased stamina, faster ambulation, decreased frequency of falls and increased muscle strength. Gower’s time decreased from 45 seconds to 15 seconds. Pediatric Berg Balance Scale score and the distance covered in the 6 minute walk test were maintained over a period of one year. No adverse effects were noted after the procedures. Stem cells are capable of differentiating into cells of many lineages and also have the potential to multiply and replenish the depleted pool of resident stem cells. Transplanted cells provide myoprotection through various paracrine mechanisms like stimulating neoangiogenesis, immuno modulation, release of anti-inflammatory cytokines, inhibiting fibrosis and stimulating resident stem cells. Along with neuro rehabilitation, stem cell therapy offers a new alternative to revolutionize the treatment received by patients with DMD.  Read more...

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked genetic myopathy characterized by progressive skeletal muscle degeneration and weakness. Recent studies have shown that stem cell derived exosomes promote angiogenic and cardioprotective function of cellular therapy. With no known cure, cellular therapy has shown some promise in altering the disease process. We report a case of DMD treated with autologous bone marrow mononuclear cell (BMMNC) transplantation followed by long term multidisciplinary rehabilitation. At follow up assessment of 4 and 13 months after cellular therapy, qualitative improvements like increased stamina, decreased calf muscle tightness, reduced toe walking, improved gait and balance were witnessed. Functional Independence Measure improved from 93 to 96. The North Star ambulatory score and Berg balance score were maintained and no functional deterioration were evident over 13 months post cellular therapy.This case report highlights the improvements in function as well as halting of progression of the disease over a period of 13 months after cellular therapy.No adverse events were observed. The improvements provide an evidence of the restorative and disease modifying benefits of cellular therapy in DMD. More randomized clinical studies will be needed to effectively establish the therapeutic benefits of cellular therapy in DMD.   Read more...

Abstract

Becker’s muscular dystrophy (BMD) is a genetic disorder characterized by progressive muscle degeneration and weakness with no definite cure. Cell therapy is emerging as a promising treatment option for BMD. Autologous bone marrow derived mononuclear cells (BMMNCs) transplantation has been shown to be safe and effective in previous preclinical studies. We treated a 21 year old boy suffering from BMD with autologous bone marrow mononuclear cells intrathecal as well as intramuscular transplantation. Pre-therapy clinical assessment showed reduced muscle power in all four limbs and trunk. He was modified independent for all the activities of daily living (ADLs) and scored 102 on Functional Independence Measure (FIM). Musculoskeletal Magnetic Resonance Imaging (MRI-MSK) revealed severe muscular atrophy and fatty replacement in the muscles. Repeat clinical assessment at follow up revealed maintained muscle power along with improvement in some muscles. North Star Ambulatory Assessment score and FIM score was maintained for over nineteen months. Repeat MRI-MSK revealed no increase in fatty infiltration in the muscles indicating halting of the progression of the disease. Thus, this report suggests the role of BMMNCs transplantation in stabilizing the condition of BMD patients. Larger clinical trials with scrupulous methodology may be suggested.   Read more...