الفهرس 
MUSCULAR DYSTROPHIESOnly 14 pages are availabe for public view
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Abstract
T
he muscular dystrophies (MDs) are a heterogeneous group of inherited disorders characterized by progressive weakness and degeneration of skeletal muscles. They have traditionally been classified by clinical presentation, mode of inheritance, age of onset, and overall progression. The development of molecular genetic mapping techniques has shown that a number of clinically similar conditions are linked to a variety of distinct single-gene disorders.So far, MDs have been mapped to at least 29 different genetic loci that give rise to at least 34 different clinical disorders, and additional information is accumulating rapidly (Richard et al., 2005).
In theory, creatine monohydrate supplementation may benefit people with muscle disorders by non-specifically enhancing muscle force output (temporal energy buffering) or the accretion of fat-free mass, assuming this is muscle, or more directly by enhancing energy shuttling, reducing intra-cellular calcium accumulation and apoptosis (Sullivan, 2000), preventing oxidative stress (primary and secondary effect), activating glycolysis and glycogenolysis, and attenuating cell death (Gualano, 2010; Klivenyi, 2004; Passaquin, 2002; Klivenyi, 1999; Pulido, 1998). Together, these considerations support the initiation of trials in people with myopathies that result in a reduction in energy charge.
This study aimed to assess the efficacy of creatine monohydrate supplementation for children with muscular dystrophy. Through many parameters including muscular strength and the ability to perform daily-life activities, effect on lean body mass, bone mineral density and content were measured by DEXA scan, also assessment of the role of supplementation on oxidative stress and myofibrillar breakdown.
The study was conducted on 30 male patients with muscular dystrophy (13 of them proven to have duchanne duchenne muscular dystrophy by gene study); Patients were recruited from the Child neurology and genetic clinics, Faculty of Medicine, Ain Shams University. All children who completed the study were Caucasians. They were all boys ranging in age from4 to 18 years, mean age was 9.2± 3.2. Each participant had the diagnosis confirmed by clinical assessment, elevated serum creatine phosphokinase (CPK) activity, eight (26.6%) of the 30 boys were dependent on a wheelchair for mobility, eighteen (60%) of them had positive family history of muscular dystrophy. The patients were randomly assigned to one of two groups,group(1) included 15 patients started the trial with the Creatine monohydrate(0.1 g/kglday) and 3 patients dropped out and group (Π) included 15patients started with the placebo and 2 patients dropped out. Exclusion criteria was Renal affection due to possible risk of renal dysfundction.
The study was approved by the Ethics Committee at Faculty of Medicine, Ain Shams University.
All patients were subjected to careful history taking, thorough clinical and neurological examination, manual muscle testing using (MRC) scale, daily life activities using (FIM), DEXA scan for (BMD, BMC, %fat and lean body mass), and blood sampling for estimation of serum level of MDA as a marker of oxidative stress, 24 hour urine collection for 3-methyl histidine as a marker of myofibrillar breakdown, all the above parameters were repeated at the end of the four months supplementation period.
In the current study, at the start there was no statistically significant difference between the two groups as regards the age, weight, height and wheelchair use.As well as there was no statistically significant difference between the two groups as regards MMT and FIM.
There was no statistically significant difference between the two groups as regards BMD, BMC, fat% and lean mass (DEXA parameters).As regards laboratory parameters, there was no statistically significant difference between the two groups as regards CPK and 3.methyl histidine3-methyl histidine but MDA was significantly lower in the placebo group(less oxidatitive stress).
On comparing initial results to follow up results in each group, there was no statistically significant difference in weight in the treatment group, on the other there was statistically significant increase in weight in the placebo group.
The results of the work revealed that there was no statistically significant difference in in MMT in the group of patients received creatine monohydrate, and there was no median of improvement of MMT, but there was statistically significant decrease in MMT in the placebo group, with 2.2% median worsening of the score, comparison between both groups (creatine versus placebo) showed no significant difference between both groups at the end of the study ,but there was statistically significant difference between both groups regarding percentage of change in (MMT).
Regarding FIM scale treatment group showed no statistically significant difference,But but the placebo group showed significant decrease in (FIM) with 2.2% median worsening of the score, comparison between both groups(creatine versus placebo) showed no significant difference between both groups,but there was statistically significant difference between both groups regarding percentage of change in FIM, implying that creatine monohydrate may prevent deterioration in muscle strength over time in patients with muscular dystrophy.
On comparing BMD before and after 4 months, in the treatment group BMD increase but was not statistically significant with 0.67% median of improvement in this group, while the placebo group showed that there was no stasticallystatistically significant difference in BMD, also there was statistically significant increase in BMC in the treatment group with no statistically significant differance in the placebo group.
Regardarding fat percentage there was statistically significant increase in fat percentage in the placebo group ((p<0.05) with no statistically significant difference in the treatment group.
Follow up of lean body mass showed no statisstically significant difference in both groups.,with non significant increase in the treatment group.
There was statistically significant decrease of MDA (median of %change =22.4%) in the treatment group, and statistically significant increase in MDA (median of %change =20%) in the placebo group.
Regarding 3 methyl histidine3-methyl histidine we didn’t found any statistically significant difference in in creatine or placebo supplemented group on follow up of patients. And there was no statistically significant difference between both groups at the end of the study. But there was 17.5% decrease of 3 methyl hstidine3-methyl histidine in treatment group and there was 4.5% decrease of 3 methyl hstidine3-methyl histidine in placebo group.
Our results support the findings that CrM supplementation is well tolerated and without side effects in patients with muscular dystrophies,it also increase BMC, decrease deterioration in muscle strength and ameliorate the increase in fat percentage in patient with muscular dystrophies,as well as decrease oxidative stress in those patients, Further investigation, on both a cellular and clinical level, is necessary to properly assess creatine’s efficacy as an alternative to existing treatments. The seeming lack of side effects, at least in short term treatments, simplifies investigations with human subjects immensely, ensuring that the putative benefits of creatine supplementation will be made accessible to patients in a timely fashion. Still, mechanistic data derived from in-vitro cell-based studies will reveal a clearer picture of the disease itself, leading to even newer therapeutic leads.However, the extent to which creatine supplementation will be effective as a treatment for muscular dystrophies remains to be seen.