Glycogen storage disease type V, also known as McArdle's disease is an autosomal recessive disorder caused by mutations in the gene that encodes myophosphorylase, an enzyme that is essential for glycogenolysis. Exercise intolerance usually develops during childhood in patients with McArdle's disease, along with pain, cramps, and fatigue in exercised muscle. These symptoms are more likely to be induced by brief, intense activities but can also occur after prolonged, low-intensity exercises. Severe muscle damage can lead to myoglobinuria and renal failure. Many patients note a "second-wind" phenomenon, whereby exercise becomes more easily tolerated after approximately 10 minutes of continued activity. This phenomenon is attributable to higher extramuscular fuel delivery to contracting muscle that partially rescues substrate-limited oxidative metabolism. In the present study Dr. Susanne Andersen and colleagues investigated whether ingesting a low dose of sucrose just before exercise would increase the availability of glucose to muscles, thus improving exercise tolerance. They aimed to achieve the benefit of sucrose administration while reducing caloric intake and to make treatment more convenient to patients by decreasing the time between sucrose ingestion and exercise. To this end, six patients were blinded to treatment and tested after ingestion of either 75 g of sucrose or a placebo 40 minutes before exercise or 37 g of sucrose or a placebo 5 minutes before exercise. Treatment effectiveness was analyzed by monitoring heart rate and perceived exertion during exercise. In all patients, sucrose ingestion 5 minutes before exercise alleviates the muscle symptoms and abolishes the second-wind phenomenon that occur during the early stages of exercise, when patients are prone to muscle injury. Compared to the 75 g dose of sucrose 40 minutes before exercise, the lower dose of sucrose was superior in providing an improved and prolonged effect on exercise tolerance in McArdle patients. Pre-exercise sucrose ingestion is not a perfect answer to McArdle disease because of the potential for causing weight gain and for potentiating the early onset of diabetes mellitus. However, until better treatments become available, the oral ingestion of sucrose before exertional activity is a reasonable approach to the management of this difficult myopathy.

Arch Neurol. 2008 Jun;65(6):786-9.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy that is characterized by rapidly progressing muscle degeneration. The disease is caused by a genetic mutation for which there is currently no cure. Research by Dr Amy Wagers and her team at Harvard University has demonstrated for the first time that transplanted muscle stem cells can both improve muscle function in a mouse model of DMD and replenish the stem cell population for use in the repair of future muscle injuries. The study was designed to test the concept that skeletal muscle precursor (SMP) cells could function as adult stem cells and that transplantation of these cells could both repair muscle tissue and regenerate the stem cell pool. The data from this new study demonstrate that regenerative muscle stem cells can be distinguished from other cells in the muscle by unique protein markers present on their surfaces. The authors used these markers to select stem cells from normal adult muscle and transferred the cells to diseased muscle of mdx mice, which carry a mutation in the same gene affected in human DMD. When engrafted into muscle of mdx mice, purified SMPs contributed to up to 94% of muscle fibers, restoring defective dystrophin gene expression and significantly improving muscle structure and contractile function. Furthermore, the transplantation of the healthy stem cells replenished the formerly diseased stem cell pool, providing a reservoir of healthy stem cells that could be re-activated to repair the muscle again during a second injury. This study will lead to other studies that will identify pathways that regulate these muscle stem cells in order to determine ways to boost the normal regenerative potential of these cells. These could include drug therapies or genomic approaches. Although stem cell technology is still in it's in infancy, this study is another step towards developing this technology into a viable treatment for people with muscle disease.

Cell. 2008 Jul 11;134(1):37-47.

Duchenne muscular dystrophy (DMD) leads to progressive deterioration in skeletal and cardiac muscle function. It has been hypothesized that the development of ventricular dysfunction associated with DMD can be altered by steroid treatment. Previous studies have shown that both load dependent and load independent measures of cardiac function can be preserved with steroid treatment. Dr. Larry Markham and colleagues have retrospectively reviewed a cohort of DMD boys undergoing cardiac evaluation before and after steroid treatment to determine the benefit of steroid treatment on the development of ventricular dysfunction in DMD. Basic medical characteristics and serial echocardiographic measures were also obtained. The data suggest that the progressive decline in cardiac function of DMD patients can be altered by steroid treatment. This study confirms the link between age and ventricular dysfunction and shows that if corticosteroid treatment is initiated prior to echocardiographic evidence of ventricular dysfunction, there is a significant beneficial effect on the anticipated development of ventricular dysfunction. Despite these observations, the authors highlight that long-term, randomized controlled clinical trails are warranted to reply to many unanswered questions.

Neuromuscul Disord. 2008 May;18(5):365-70.

Laminopathies comprise a group of inherited diseases with variable clinical phenotypes. They are caused by mutations in the lamin complexes (LMNA) of the nuclear envelope. Prominent features of these human disorders are muscular dystrophy, cardiomyopathy, lipodystrophy, and progeria. Most of these diseases have postnatal onset, progressively developed during childhood or adolescence. Early onset at birth or during infancy has rarely been reported. In this paper, Dr. Susana Quijano-Roy and colleagues report for the first time, the involvement of a nuclear envelope protein in a congenital muscular dystrophy (CMD). They describe the clinical, morphological and genetic characteristics in 15 unrelated LMNA mutated children affected with a distinct and early progressive form of muscular dystrophy. Mild-to-severe dystrophic changes were observed in many of the biopsies, serum CK level was generally increased and there was a fairly rapid disease progression. Two clinical phenotypes were evident: a subgroup of patients with severe weakness and minimal or absent motor development and a larger subgroup with milder disease who developed dropped-headed syndrome after acquiring head control. LMNA gene screening identified heterozygous de novo LMNA mutations in all patients. Dominant de novo mutations in the LMNA gene can be associated with a severe progressive myopathy with presentation in the first year of life, associated with a distinct pattern of weakness, invariable respiratory insufficiency and risk for heart rhythm disturbances. The authors suggest that this early onset phenotype best be classified as a CMD, thus further increasing the spectrum of laminopathies. This study was partly supported by the AFM.

Ann Neurol. 2008 Jun 12. [Epub ahead of print]